Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas

doi:10.2174/1389450120666191016143836
摘要

上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤。尽管对基于铂的标准治疗的初始应答率为70-80％，但随着化学抗药性和复发的发展，晚期EOC疾病的长期应答极少实现，导致总生存率低于45％。 EOC的异质性带来了其他挑战，这反映了至少五种组织学亚型，每种亚型具有不同的基本分子特征和临床病理学，对治疗效果和治疗具有重要意义。自上个十年以来，基因组学，蛋白质组学和病理学技术已被用于寻找可靠的临床标志物，这些标志物可以识别对标准化学疗法敏感的患者，并对患者进行分层以寻求更合适的靶向疗法。这些努力已经确定了几种具有预后价值的分子标志物，这些标志物已被证实是生物标志物，例如BRCA和KRAS突变，或者目前正在临床试验中进行研究，例如CD8 T细胞，免疫检查点抑制剂和孕激素受体。生物标志物研究的最新进展还揭示了扩大治疗选择的新靶标，引入了聚（ADP-核糖）聚合酶（PARP）抑制剂，抗血管生成剂，靶向信号通路的抑制剂和免疫疗法，以改善维持疗法或增强一线治疗治疗。这篇综述总结了目前在临床上使用或正在评估中的生物标志物，证明有潜力为患者选择治疗功效和预测对EOC疗法的反应提供指导，尤其着重于浆液亚型，包括高级别和低级别浆液性癌。
关键词: BRCA，标志物，PARP抑制剂，免疫治疗，抗血管生成治疗，激素治疗，长期生存，靶向治疗，高级别浆液，低级别浆液。
« Previous
图形摘要

[1] 
Bowtell DD, Böhm S, Ahmed AA, et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer  2015; 15(11): 668-79.
[http://dx.doi.org/10.1038/nrc4019] [PMID:  26493647] 
[2] 
Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers  2016; 2: 16061.
[http://dx.doi.org/10.1038/nrdp.2016.61] [PMID:  27558151] 
[3] 
Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet  2019; 393(10177): 1240-53.
[http://dx.doi.org/10.1016/S0140-6736(18)32552-2] [PMID:  30910306] 
[4] 
Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-grade serous ovarian cancer: basic sciences, Clinical and Therapeutic Standpoints. Int J Mol Sci  2019; 20(4) E952
[http://dx.doi.org/10.3390/ijms20040952] [PMID:  30813239] 
[5] 
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin  2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID:  30207593] 
[6] 
Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med  2017; 14(1): 9-32.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0084] [PMID:  28443200] 
[7] 
El Bairi K, Atanasov AG, Amrani M, Afqir S. The arrival of predictive biomarkers for monitoring therapy response to natural compounds in cancer drug discovery. Biomed Pharmacother  2019; 109: 2492-8.
[http://dx.doi.org/10.1016/j.biopha.2018.11.097] [PMID:  30551510] 
[8] 
El Bairi K, Kandhro AH, Gouri A, et al. Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer. Cell Oncol (Dordr)  2017; 40(2): 105-18.
[http://dx.doi.org/10.1007/s13402-016-0309-1] [PMID:  27981507] 
[9] 
Singh N, McCluggage WG, Gilks CB. High-grade serous carcinoma of tubo-ovarian origin: recent developments. Histopathology  2017; 71(3): 339-56.
[http://dx.doi.org/10.1111/his.13248] [PMID:  28477361] 
[10] 
Medeiros F, Muto MG, Lee Y, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol  2006; 30(2): 230-6.
[http://dx.doi.org/10.1097/01.pas.0000180854.28831.77] [PMID:  16434898] 
[11] 
Labidi-Galy SI, Papp E, Hallberg D, et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun  2017; 8(1): 1093.
[http://dx.doi.org/10.1038/s41467-017-00962-1] [PMID:  29061967] 
[12] 
Visvanathan K, Shaw P, May BJ, et al. Fallopian tube lesions in women at high risk for ovarian cancer: a multicenter study. Cancer Prev Res (Phila)  2018; 11(11): 697-706.
[http://dx.doi.org/10.1158/1940-6207.CAPR-18-0009] [PMID:  30232083] 
[13] 
Webber K, Friedlander M. Chemotherapy for epithelial ovarian, fallopian tube and primary peritoneal cancer. Best Pract Res Clin Obstet Gynaecol  2017; 41: 126-38.
[http://dx.doi.org/10.1016/j.bpobgyn.2016.11.004] [PMID:  28027849] 
[14] 
Previs RA, Sood AK, Mills GB, Westin SN. The rise of genomic profiling in ovarian cancer. Expert Rev Mol Diagn  2016; 16(12): 1337-51.
[http://dx.doi.org/10.1080/14737159.2016.1259069] [PMID:  27828713] 
[15] 
Hanker LC, Loibl S, Burchardi N, et al. AGO and GINECO study group. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol  2012; 23(10): 2605-12.
[http://dx.doi.org/10.1093/annonc/mds203] [PMID:  22910840] 
[16] 
wilson mk, pujade-lauraine e, aoki d, et al. fifth ovarian cancer consensus conference of the gynecologic cancer intergroup: recurrent disease. Ann Oncol  2017; 28(4): 727-32.
[PMID:  27993805] 
[17] 
Teer JK, Yoder S, Gjyshi A, Nicosia SV, Zhang C, Monteiro ANA. Mutational heterogeneity in non-serous ovarian cancers. Sci Rep  2017; 7(1): 9728.
[http://dx.doi.org/10.1038/s41598-017-10432-9] [PMID:  28852190] 
[18] 
Verhaak RG, Tamayo P, Yang JY, et al. Cancer Genome Atlas Research Network. Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. J Clin Invest  2013; 123(1): 517-25.
[PMID:  23257362] 
[19] 
Doherty JA, Peres LC, Wang C, Way GP, Greene CS, Schildkraut JM. Challenges and opportunities in studying the epidemiology of ovarian cancer subtypes. Curr Epidemiol Rep  2017; 4(3): 211-20.
[http://dx.doi.org/10.1007/s40471-017-0115-y] [PMID:  29226065] 
[20] 
Leary AF, Quinn M, Fujiwara K, et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours. Ann Oncol  2017; 28(4): 718-26.
[PMID:  27993794] 
[21] 
Vang R, Hannibal CG, Junge J, Frederiksen K, Kjaer SK, Kurman RJ. Long-term behavior of serous borderline tumors subdivided into atypical proliferative tumors and noninvasive low-grade carcinomas: a population-based clinicopathologic study of 942 cases. Am J Surg Pathol  2017; 41(6): 725-37.
[http://dx.doi.org/10.1097/PAS.0000000000000824] [PMID:  28248817] 
[22] 
Le Page C, Rahimi K, Köbel M, et al. Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers. BMC Cancer  2018; 18(1): 347.
[http://dx.doi.org/10.1186/s12885-018-4242-8] [PMID:  29587661] 
[23] 
Kurman RJ, Shih IeM. The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded. Am J Pathol  2016; 186(4): 733-47.
[http://dx.doi.org/10.1016/j.ajpath.2015.11.011] [PMID:  27012190] 
[24] 
Köbel M, Rahimi K, Rambau PF, et al. An Immunohistochemical Algorithm for Ovarian Carcinoma Typing. Int J Gynecol Pathol  2016; 35(5): 430-41.
[http://dx.doi.org/10.1097/PGP.0000000000000274] [PMID:  26974996] 
[25] 
Vergote IB, Van Nieuwenhuysen E, Vanderstichele A. How to select neoadjuvant chemotherapy or primary debulking surgery in patients with stage iiic or iv ovarian carcinoma. J Clin Oncol  2016; 34(32): 3827-8.
[http://dx.doi.org/10.1200/JCO.2016.69.7458] [PMID:  27646940] 
[26] 
Chang SJ, Bristow RE, Chi DS, Cliby WA. Role of aggressive surgical cytoreduction in advanced ovarian cancer. J Gynecol Oncol  2015; 26(4): 336-42.
[http://dx.doi.org/10.3802/jgo.2015.26.4.336] [PMID:  26197773] 
[27] 
Provencher DM, Gallagher CJ, Parulekar WR, et al. OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer. Ann Oncol  2018; 29(2): 431-8.
[http://dx.doi.org/10.1093/annonc/mdx754] [PMID:  29186319] 
[28] 
Lavoue V, Huchon C, Akladios C, et al. Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up). J Gynecol Obstet Hum Reprod  2019; 48(6): 379-86.
[http://dx.doi.org/10.1016/j.jogoh.2019.03.018] [PMID:  30936025] 
[29] 
Zhang G, Zhu Y, Liu C, Chao G, Cui R, Zhang Z. The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis. J Ovarian Res  2019; 12(1): 33.
[http://dx.doi.org/10.1186/s13048-019-0509-1] [PMID:  30995948] 
[30] 
Naumann RW, Coleman RL, Brown J, Moore KN. Phase III trials in ovarian cancer: The evolving landscape of front line therapy. Gynecol Oncol  2019; 153(2): 436-44.
[http://dx.doi.org/10.1016/j.ygyno.2019.02.008] [PMID:  30765149] 
[31] 
Lee S, Piskorz AM, Le Page C, et al. Calibration and optimization of p53, wt1, and napsin a immunohistochemistry ancillary tests for histotyping of ovarian carcinoma: canadian immunohistochemistry quality control (ciqc) experience. Int J Gynecol Pathol  2016; 35(3): 209-21.
[http://dx.doi.org/10.1097/PGP.0000000000000251] [PMID:  26598982] 
[32] 
Sölétormos G, Duffy MJ, Othman Abu Hassan S, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the european group on tumor markers. Int J Gynecol Cancer  2016; 26(1): 43-51.
[http://dx.doi.org/10.1097/IGC.0000000000000586] [PMID:  26588231] 
[33] 
Le Page C, Köbel M, de Ladurantaye M, et al. Specimen quality evaluation in Canadian biobanks participating in the COEUR repository. Biopreserv Biobank  2013; 11(2): 83-93.
[http://dx.doi.org/10.1089/bio.2012.0044] [PMID:  24845429] 
[34] 
Chenevix-Trench G, Milne RL, Antoniou AC, Couch FJ, Easton DF, Goldgar DE. CIMBA. An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Breast Cancer Res  2007; 9(2): 104.
[http://dx.doi.org/10.1186/bcr1670] [PMID:  17466083] 
[35] 
Swerdlow AJ, Harvey CE, Milne RL, et al. The National Cancer Institute Cohort Consortium: An International Pooling Collaboration of 58 Cohorts from 20 Countries. Cancer Epidemiol Biomarkers Prev  2018; 27(11): 1307-19.
[http://dx.doi.org/10.1158/1055-9965.EPI-18-0182] [PMID:  30018149] 
[36] 
Fortner RT, Poole EM, Wentzensen NA, et al. Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium. Int J Cancer  2019; 145(1): 58-69.
[http://dx.doi.org/10.1002/ijc.32075] [PMID:  30561796] 
[37] 
Bolton KL, Chenevix-Trench G, Goh C, et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA  2012; 307(4): 382-90.
[http://dx.doi.org/10.1001/jama.2012.20] [PMID:  22274685] 
[38] 
Candido-dos-Reis FJ, Song H, Goode EL, et al. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clin Cancer Res  2015; 21(3): 652-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2497] [PMID:  25398451] 
[39] 
Rebbeck TR, Mitra N, Wan F, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA  2015; 313(13): 1347-61.
[http://dx.doi.org/10.1001/jama.2014.5985] [PMID:  25849179] 
[40] 
Liu J, Lichtenberg T, Hoadley KA, et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell  2018; 173(2): 400-16. e411
[http://dx.doi.org/10.1016/j.cell.2018.02.052] 
[41] 
Yang WL, Lu Z, Bast RC Jr. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn  2017; 17(6): 577-91.
[http://dx.doi.org/10.1080/14737159.2017.1326820] [PMID:  28468520] 
[42] 
Rustin GJ. Use of CA-125 to assess response to new agents in ovarian cancer trials. J Clin Oncol  2003; 21(10)(Suppl.): 187s-93s.
[http://dx.doi.org/10.1200/JCO.2003.01.223] [PMID:  12743133] 
[43] 
Rustin GJ, Hall MR. Is CA125 useful in monitoring patients with platinum-resistant ovarian cancer? Ann Oncol  2016; 27(8): 1365-6.
[http://dx.doi.org/10.1093/annonc/mdw253] [PMID:  27358387] 
[44] 
Vallius T, Hynninen J, Auranen A, et al. Postoperative human epididymis protein 4 predicts primary therapy outcome in advanced epithelial ovarian cancer. Tumour Biol  2017; 39(2) 1010428317691189
[http://dx.doi.org/10.1177/1010428317691189] [PMID:  28218038] 
[45] 
Chudecka-Głaz A, Cymbaluk-Płoska A, Wężowska M, Menkiszak J. Could HE4 level measurements during first-line chemotherapy predict response to treatment among ovarian cancer patients? PLoS One  2018; 13(3) e0194270
[http://dx.doi.org/10.1371/journal.pone.0194270] [PMID:  29584739] 
[46] 
Ferraro S, Panteghini M. Making new biomarkers a reality: the case of serum human epididymis protein 4. Clin Chem Lab Med 2018.
[PMID: 30511925] 
[47] 
Cao H, You D, Lan Z, Ye H, Hou M, Xi M. Prognostic value of serum and tissue HE4 expression in ovarian cancer: a systematic review with meta-analysis of 90 studies. Expert Rev Mol Diagn  2018; 18(4): 371-83.
[http://dx.doi.org/10.1080/14737159.2018.1457436] [PMID:  29569984] 
[48] 
Nassir M, Guan J, Luketina H, et al. The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients-results from the OVCAD study. Tumour Biol  2016; 37(3): 3009-16.
[http://dx.doi.org/10.1007/s13277-015-4031-9] [PMID:  26419591] 
[49] 
Hamed EO, Ahmed H, Sedeek OB, Mohammed AM, Abd-Alla AA, Abdel Ghaffar HM. Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response. Diagn Pathol  2013; 8: 11.
[http://dx.doi.org/10.1186/1746-1596-8-11] [PMID:  23343214] 
[50] 
Kalli KR, Oberg AL, Keeney GL, et al. Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol  2008; 108(3): 619-26.
[http://dx.doi.org/10.1016/j.ygyno.2007.11.020] [PMID:  18222534] 
[51] 
Köbel M, Madore J, Ramus SJ, et al. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study. Br J Cancer  2014; 111(12): 2297-307.
[http://dx.doi.org/10.1038/bjc.2014.567] [PMID:  25349970] 
[52] 
Basal E, Eghbali-Fatourechi GZ, Kalli KR, et al. Functional folate receptor alpha is elevated in the blood of ovarian cancer patients. PLoS One  2009; 4(7) e6292
[http://dx.doi.org/10.1371/journal.pone.0006292] [PMID:  19617914] 
[53] 
Leung F, Dimitromanolakis A, Kobayashi H, Diamandis EP, Kulasingam V. Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients. Clin Biochem  2013; 46(15): 1462-8.
[http://dx.doi.org/10.1016/j.clinbiochem.2013.03.010] [PMID:  23528302] 
[54] 
Farran B, Albayrak S, Abrams J, et al. Serum folate receptor α (sFR) in ovarian cancer diagnosis and surveillance. Cancer Med  2019; 8(3): 920-7.
[http://dx.doi.org/10.1002/cam4.1944] [PMID:  30761774] 
[55] 
Shen DW, Su A, Liang XJ, Pai-Panandiker A, Gottesman MM. Reduced expression of small GTPases and hypermethylation of the folate binding protein gene in cisplatin-resistant cells. Br J Cancer  2004; 91(2): 270-6.
[http://dx.doi.org/10.1038/sj.bjc.6601956] [PMID:  15199393] 
[56] 
Huang MJ, Zhang W, Wang Q, Yang ZJ, Liao SB, Li L. FOLR1 increases sensitivity to cisplatin treatment in ovarian cancer cells. J Ovarian Res  2018; 11(1): 15.
[http://dx.doi.org/10.1186/s13048-018-0387-y] [PMID:  29433550] 
[57] 
Vergote IB, Marth C, Coleman RL. Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications. Cancer Metastasis Rev  2015; 34(1): 41-52.
[http://dx.doi.org/10.1007/s10555-014-9539-8] [PMID:  25564455] 
[58] 
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature  2011; 474(7353): 609-15.
[http://dx.doi.org/10.1038/nature10166] [PMID:  21720365] 
[59] 
Yang D, Khan S, Sun Y, et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA  2011; 306(14): 1557-65.
[http://dx.doi.org/10.1001/jama.2011.1456] [PMID:  21990299] 
[60] 
Gee ME, Faraahi Z, McCormick A, Edmondson RJ. DNA damage repair in ovarian cancer: unlocking the heterogeneity. J Ovarian Res  2018; 11(1): 50.
[http://dx.doi.org/10.1186/s13048-018-0424-x] [PMID:  29925418] 
[61] 
Damia G, Broggini M. platinum resistance in ovarian cancer: role of dna repair. Cancers (Basel)  2019; 11(1) E119
[http://dx.doi.org/10.3390/cancers11010119] [PMID:  30669514] 
[62] 
Mukhopadhyay A, Plummer ER, Elattar A, et al. Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum, and survival. Cancer Res  2012; 72(22): 5675-82.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0324] [PMID:  23066035] 
[63] 
Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov  2015; 5(11): 1137-54.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0714] [PMID:  26463832] 
[64] 
Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res  2014; 20(3): 764-75.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2287] [PMID:  24240112] 
[65] 
Mylavarapu S, Das A, Roy M. Role of brca mutations in the modulation of response to platinum therapy. Front Oncol  2018; 8: 16.
[http://dx.doi.org/10.3389/fonc.2018.00016] [PMID:  29459887] 
[66] 
Xu K, Yang S, Zhao Y. Prognostic significance of BRCA mutations in ovarian cancer: an updated systematic review with meta-analysis. Oncotarget  2017; 8(1): 285-302.
[http://dx.doi.org/10.18632/oncotarget.12306] [PMID:  27690218] 
[67] 
Cook SA, Tinker AV. PARP inhibitors and the evolving landscape of ovarian cancer management: a review. BioDrugs  2019; 33(3): 255-73.
[http://dx.doi.org/10.1007/s40259-019-00347-4] [PMID:  30895466] 
[68] 
Capoluongo E, Scambia G, Nabholtz JM. Main implications related to the switch to BRCA1/2 tumor testing in ovarian cancer patients: a proposal of a consensus. Oncotarget  2018; 9(28): 19463-8.
[http://dx.doi.org/10.18632/oncotarget.24728] [PMID:  29731958] 
[69] 
Mafficini A, Simbolo M, Parisi A, et al. BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by next-generation sequencing. Oncotarget  2016; 7(2): 1076-83.
[http://dx.doi.org/10.18632/oncotarget.6834] [PMID:  26745875] 
[70] 
Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer  2016; 16(2): 110-20.
[http://dx.doi.org/10.1038/nrc.2015.21] [PMID:  26775620] 
[71] 
da Cunha Colombo Bonadio RR, Fogace RN, Miranda VC, Diz MDPE. Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (São Paulo)  2018; 73(Suppl. 1). e450s
[PMID:  30133561] 
[72] 
Wiedemeyer WR, Beach JA, Karlan BY. Reversing platinum resistance in high-grade serous ovarian carcinoma: targeting brca and the homologous recombination system. Front Oncol  2014; 4: 34.
[http://dx.doi.org/10.3389/fonc.2014.00034] [PMID:  24624361] 
[73] 
Norquist B, Wurz KA, Pennil CC, et al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol  2011; 29(22): 3008-15.
[http://dx.doi.org/10.1200/JCO.2010.34.2980] [PMID:  21709188] 
[74] 
Patch AM, Christie EL, Etemadmoghadam D, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature  2015; 521(7553): 489-94.
[http://dx.doi.org/10.1038/nature14410] [PMID:  26017449] 
[75] 
Christie EL, Bowtell DDL. Acquired chemotherapy resistance in ovarian cancer. Ann Oncol  2017; 28(suppl_8): viii13-5.
[http://dx.doi.org/10.1093/annonc/mdx446] 
[76] 
Madariaga A, Lheureux S, Oza AM. Tailoring ovarian cancer treatment: implications of brca1/2 mutations. Cancers (Basel)  2019; 11(3) E416
[http://dx.doi.org/10.3390/cancers11030416] [PMID:  30909618] 
[77] 
Vanderstichele A, Busschaert P, Olbrecht S, Lambrechts D, Vergote I. Genomic signatures as predictive biomarkers of homologous recombination deficiency in ovarian cancer. Eur J Cancer  2017; 86: 5-14.
[http://dx.doi.org/10.1016/j.ejca.2017.08.029] [PMID:  28950147] 
[78] 
Abkevich V, Timms KM, Hennessy BT, et al. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer  2012; 107(10): 1776-82.
[http://dx.doi.org/10.1038/bjc.2012.451] [PMID:  23047548] 
[79] 
Tumiati M, Hietanen S, Hynninen J, et al. A functional homologous recombination assay predicts primary chemotherapy res- ponse and long-term survival in ovarian cancer patients. Clin Cancer Res  2018; 24(18): 4482-93.
[PMID:  29858219] 
[80] 
Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med  2016; 375(22): 2154-64.
[http://dx.doi.org/10.1056/NEJMoa1611310] [PMID:  27717299] 
[81] 
Telli ML, Timms KM, Reid J, et al. Homologous recombination deficiency (hrd) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res  2016; 22(15): 3764-73.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2477] [PMID:  26957554] 
[82] 
Stronach EA, Paul J, Timms KM, et al. Biomarker assessment of hr deficiency, tumor brca1/2 mutations, and ccne1 copy number in ovarian cancer: associations with clinical outcome following platinum monotherapy. Mol Cancer Res  2018; 16(7): 1103-11.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0034] [PMID:  29724815] 
[83] 
Hurley RM, Wahner Hendrickson AE, Visscher DW, et al. 53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer. Gynecol Oncol  2019; 153(1): 127-34.
[http://dx.doi.org/10.1016/j.ygyno.2019.01.015] [PMID:  30686551] 
[84] 
Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther  2015; 16(6): 807-20.
[http://dx.doi.org/10.1080/15384047.2015.1040960] [PMID:  25894333] 
[85] 
Drakes ML, Stiff PJ. Regulation of ovarian cancer prognosis by immune cells in the tumor microenvironment. Cancers (Basel)  2018; 10(9) E302
[http://dx.doi.org/10.3390/cancers10090302] [PMID:  30200478] 
[86] 
Wouters MCA, Nelson BH. Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer. Clin Cancer Res  2018; 24(24): 6125-35.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-1481] [PMID:  30049748] 
[87] 
Galon J, Pagès F, Marincola FM, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med  2012; 10: 205.
[http://dx.doi.org/10.1186/1479-5876-10-205] [PMID:  23034130] 
[88] 
Bösmüller HC, Wagner P, Peper JK, et al. Combined immunoscore of cd103 and cd3 identifies long-term survivors in high-grade serous ovarian cancer. Int J Gynecol Cancer  2016; 26(4): 671-9.
[http://dx.doi.org/10.1097/IGC.0000000000000672] [PMID:  26905331] 
[89] 
Hao D, Liu J, Chen M, et al. Immunogenomic analyses of advanced serous ovarian cancer reveal immune score is a strong prognostic factor and an indicator of chemosensitivity. Clin Cancer Res  2018; 24(15): 3560-71.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3862] [PMID:  29661778] 
[90] 
Nelson BH, Jazaeri AA. Immunotherapy for gynecological cancers: opportunities abound. Gynecol Oncol  2017; 145(3): 411-2.
[http://dx.doi.org/10.1016/j.ygyno.2017.05.003] [PMID:  28552394] 
[91] 
Rodriguez GM, Galpin KJC, McCloskey CW, Vanderhyden BC. The tumor microenvironment of epithelial ovarian cancer and its influence on response to immunotherapy. Cancers (Basel)  2018; 10(8) E242
[http://dx.doi.org/10.3390/cancers10080242] [PMID:  30042343] 
[92] 
Goode EL, Block MS, Kalli KR, et al. Dose-response association of cd8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol  2017; 3(12) e173290
[http://dx.doi.org/10.1001/jamaoncol.2017.3290] [PMID:  29049607] 
[93] 
Lieber S, Reinartz S, Raifer H, et al. Prognosis of ovarian cancer is associated with effector memory CD8+ T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells. OncoImmunology  2018; 7(5) e1424672
[http://dx.doi.org/10.1080/2162402X.2018.1424672] [PMID:  29721385] 
[94] 
Lo CS, Sanii S, Kroeger DR, et al. Neoadjuvant chemotherapy of ovarian cancer results in three patterns of tumor-infiltrating lymphocyte response with distinct implications for immunothe-rapy. Clin Cancer Res  2017; 23(4): 925-34.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-1433] [PMID:  27601594] 
[95] 
Webb JR, Milne K, Kroeger DR, Nelson BH. PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. Gynecol Oncol  2016; 141(2): 293-302.
[http://dx.doi.org/10.1016/j.ygyno.2016.03.008] [PMID:  26972336] 
[96] 
Webb JR, Milne K, Nelson BH. PD-1 and cd103 are widely coexpressed on prognostically favorable intraepithelial cd8 t cells in human ovarian cancer. Cancer Immunol Res  2015; 3(8): 926-35.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0239] [PMID:  25957117] 
[97] 
Au KK, Le Page C, Ren R, et al. STAT1-associated intratumoural TH1 immunity predicts chemotherapy resistance in high-grade serous ovarian cancer. J Pathol Clin Res  2016; 2(4): 259-70.
[http://dx.doi.org/10.1002/cjp2.55] [PMID:  27917296] 
[98] 
Zhang AW, McPherson A, Milne K, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell  2018; 173(3): 1755-69. e1722
[http://dx.doi.org/10.1016/j.cell.2018.03.073] 
[99] 
Wang W, Kryczek I, Dostál L, et al. Effector t cells abrogate stroma-mediated chemoresistance in ovarian cancer. Cell  2016; 165(5): 1092-105.
[http://dx.doi.org/10.1016/j.cell.2016.04.009] [PMID:  27133165] 
[100] 
Strickland KC, Howitt BE, Shukla SA, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget  2016; 7(12): 13587-98.
[http://dx.doi.org/10.18632/oncotarget.7277] [PMID:  26871470] 
[101] 
Modugno F, Laskey R, Smith AL, Andersen CL, Haluska P, Oesterreich S. Hormone response in ovarian cancer: time to reconsider as a clinical target? Endocr Relat Cancer  2012; 19(6): R255-79.
[http://dx.doi.org/10.1530/ERC-12-0175] [PMID:  23045324] 
[102] 
Voutsadakis IA. On adjuvant hormone therapy in epithelial ovarian cancer. J Clin Oncol  2016; 34(17): 2070-1.
[http://dx.doi.org/10.1200/JCO.2015.66.3245] [PMID:  27001577] 
[103] 
Sieh W, Köbel M, Longacre TA, et al. Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. Lancet Oncol  2013; 14(9): 853-62.
[http://dx.doi.org/10.1016/S1470-2045(13)70253-5] [PMID:  23845225] 
[104] 
Le Page C, Rahimi K, Mes-Masson AM, Köbel M. Prognostic value of progesterone receptor expression in tubo-ovarian high-grade serous carcinoma of the COEUR cohort. Histopathology  2019; 74(4): 663-6.
[http://dx.doi.org/10.1111/his.13784] [PMID:  30403298] 
[105] 
Le Page C, Provencher D, Maugard CM, Ouellet V, Mes-Masson AM. Signature of a silent killer: expression profiling in epithelial ovarian cancer. Expert Rev Mol Diagn  2004; 4(2): 157-67.
[http://dx.doi.org/10.1586/14737159.4.2.157] [PMID:  14995903] 
[106] 
Konecny GE, Winterhoff B, Wang C. Gene-expression signatures in ovarian cancer: Promise and challenges for patient stratification. Gynecol Oncol  2016; 141(2): 379-85.
[http://dx.doi.org/10.1016/j.ygyno.2016.01.026] [PMID:  26827964] 
[107] 
Bonome T, Levine DA, Shih J, et al. A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res  2008; 68(13): 5478-86.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6595] [PMID:  18593951] 
[108] 
Madore J, Ren F, Filali-Mouhim A, et al. Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma. J Pathol  2010; 220(3): 392-400.
[PMID: 19967725] 
[109] 
Meinhold-Heerlein I, Bauerschlag D, Hilpert F, et al. Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential. Oncogene  2005; 24(6): 1053-65.
[http://dx.doi.org/10.1038/sj.onc.1208298] [PMID:  15558012] 
[110] 
Tan TZ, Miow QH, Huang RY, et al. Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. EMBO Mol Med  2013; 5(7): 1051-66.
[http://dx.doi.org/10.1002/emmm.201201823] [PMID:  23666744] 
[111] 
Cook DP, Vanderhyden BC. Ovarian cancer and the evolution of subtype classifications using transcriptional profiling. Biol Reprod 2019. ioz099
[http://dx.doi.org/10.1093/biolre/ioz099] [PMID:  31187121] 
[112] 
Tothill RW, Tinker AV, George J, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res  2008; 14(16): 5198-208.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0196] [PMID:  18698038] 
[113] 
Schildkraut JM, Iversen ES, Akushevich L, et al. Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev  2013; 22(10): 1709-21.
[http://dx.doi.org/10.1158/1055-9965.EPI-13-0192] [PMID:  23917454] 
[114] 
Wang C, Armasu SM, Kalli KR, et al. Pooled clustering of high-grade serous ovarian cancer gene expression leads to novel consensus subtypes associated with survival and surgical outcomes. Clin Cancer Res  2017; 23(15): 4077-85.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0246] [PMID:  28280090] 
[115] 
Konecny GE, Wang C, Hamidi H, et al. Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer. J Natl Cancer Inst  2014; 106(10) dju249
[http://dx.doi.org/10.1093/jnci/dju249] [PMID:  25269487] 
[116] 
Chen GM, Kannan L, Geistlinger L, et al. Consensus on molecular subtypes of high-grade serous ovarian carcinoma. Clin Cancer Res  2018; 24(20): 5037-47.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0784] [PMID:  30084834] 
[117] 
Leong HS, Galletta L, Etemadmoghadam D, et al. Efficient molecular subtype classification of high-grade serous ovarian cancer. J Pathol  2015; 236(3): 272-7.
[http://dx.doi.org/10.1002/path.4536] [PMID:  25810134] 
[118] 
Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol  2017; 18(1): 75-87.
[http://dx.doi.org/10.1016/S1470-2045(16)30559-9] [PMID:  27908594] 
[119] 
McCormick A, Donoghue P, Dixon M, et al. Ovarian cancers harbor defects in nonhomologous end joining resulting in res- istance to rucaparib. Clin Cancer Res  2017; 23(8): 2050-60.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0564] [PMID:  27702817] 
[120] 
Goodwin JF, Knudsen KE. Beyond DNA repair: DNA-PK function in cancer. Cancer Discov  2014; 4(10): 1126-39.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0358] [PMID:  25168287] 
[121] 
Dungl DA, Maginn EN, Stronach EA. Preventing damage limitation: targeting dna-pkcs and dna double-strand break repair pathways for ovarian cancer therapy. Front Oncol  2015; 5: 240.
[http://dx.doi.org/10.3389/fonc.2015.00240] [PMID:  26579492] 
[122] 
Stronach EA, Chen M, Maginn EN, et al. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance. Neoplasia  2011; 13(11): 1069-80.
[http://dx.doi.org/10.1593/neo.111032] [PMID:  22131882] 
[123] 
Zhang Z, Xiang Q, Mu G, et al. XRCC1 polymorphism and overall survival in ovarian cancer patients treated with platinum-based chemotherapy: A systematic review and MOOSE-compliant meta-analysis. Medicine (Baltimore)  2018; 97(45) e12996
[http://dx.doi.org/10.1097/MD.0000000000012996] [PMID:  30407287] 
[124] 
Zhai XH, Huang J, Wu FX, Zhu DY, Wang AC. Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian Carcinoma Patients Treated with Chemotherapy. Oncol Res Treat  2016; 39(7-8): 440-6.
[http://dx.doi.org/10.1159/000447337] [PMID:  27487108] 
[125] 
Mucaki EJ, Zhao JZL, Lizotte DJ, Rogan PK. Predicting responses to platin chemotherapy agents with biochemically-inspired machine learning. Signal Transduct Target Ther  2019; 4: 1.
[http://dx.doi.org/10.1038/s41392-018-0034-5] [PMID:  30652029] 
[126] 
Xu Q, Ding YY, Song LX, Xu JF. Correlation of UGT1A1 and ERCC1 gene polymorphisms with the outcome of combined irinotecan plus cisplatin treatment in recurrent ovarian cancer. Genet Mol Res  2015; 14(2): 7241-7.
[http://dx.doi.org/10.4238/2015.June.29.17] [PMID:  26125934] 
[127] 
Stordal B, Davey R. ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair. Cancer Chemother Pharmacol  2009; 63(4): 661-72.
[http://dx.doi.org/10.1007/s00280-008-0783-x] [PMID:  18575867] 
[128] 
McNeil EM, Astell KR, Ritchie AM, et al. Inhibition of the ERCC1-XPF structure-specific endonuclease to overcome cancer chemoresistance. DNA Repair (Amst)  2015; 31: 19-28.
[http://dx.doi.org/10.1016/j.dnarep.2015.04.002] [PMID:  25956741] 
[129] 
Ganzinelli M, Mariani P, Cattaneo D, et al. Expression of DNA repair genes in ovarian cancer samples: biological and clinical considerations. Eur J Cancer  2011; 47(7): 1086-94.
[http://dx.doi.org/10.1016/j.ejca.2010.11.029] [PMID:  21216588] 
[130] 
Du P, Zhang X, Liu H, Chen L. Lentivirus-Mediated RNAi silencing targeting ERCC1 reverses cisplatin resistance in cisplatin-resistant ovarian carcinoma cell line. DNA Cell Biol  2015; 34(7): 497-502.
[http://dx.doi.org/10.1089/dna.2015.2805] [PMID:  25941922] 
[131] 
Caiola E, Porcu L, Fruscio R, et al. DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian cancer. Pharmacogenomics J  2013; 13(2): 159-72.
[http://dx.doi.org/10.1038/tpj.2011.50] [PMID:  22158331] 
[132] 
Liu SC, Lin H, Huang CC, et al. Prognostic role of excision repair cross complementing-1 and topoisomerase-1 expression in epithelial ovarian cancer. Taiwan J Obstet Gynecol  2016; 55(2): 213-9.
[http://dx.doi.org/10.1016/j.tjog.2016.02.011] [PMID:  27125404] 
[133] 
Liu J, Zhang L, Mao P, et al. Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer. Oncotarget  2017; 8(49): 85759-71.
[http://dx.doi.org/10.18632/oncotarget.20482] [PMID:  29156754] 
[134] 
Mesquita KA, Alabdullah M, Griffin M, et al. ERCC1-XPF deficiency is a predictor of olaparib induced synthetic lethality and platinum sensitivity in epithelial ovarian cancers. Gynecol Oncol  2019; 153(2): 416-24.
[http://dx.doi.org/10.1016/j.ygyno.2019.02.014] [PMID:  30797591] 
[135] 
Scurry J, van Zyl B, Gulliver D, et al. Nucleotide excision repair protein ERCC1 and tumour-infiltrating lymphocytes are potential biomarkers of neoadjuvant platinum resistance in high grade serous ovarian cancer. Gynecol Oncol  2018; 151(2): 306-10.
[http://dx.doi.org/10.1016/j.ygyno.2018.08.030] [PMID:  30194007] 
[136] 
Drakes ML, Mehrotra S, Aldulescu M, et al. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer. J Ovarian Res  2018; 11(1): 43.
[http://dx.doi.org/10.1186/s13048-018-0414-z] [PMID:  29843813] 
[137] 
Wang L. Prognostic effect of programmed death-ligand 1 (PD-L1) in ovarian cancer: a systematic review, meta-analysis and bioinformatics study. J Ovarian Res  2019; 12(1): 37.
[http://dx.doi.org/10.1186/s13048-019-0512-6] [PMID:  31039792] 
[138] 
Lin H, Wei S, Hurt EM, et al. Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. J Clin Invest  2018; 128(2): 805-15.
[http://dx.doi.org/10.1172/JCI96113] [PMID:  29337305] 
[139] 
Larionova I, Cherdyntseva N, Liu T, Patysheva M, Rakina M, Kzhyshkowska J. Interaction of tumor-associated macrophages and cancer chemotherapy. OncoImmunology  2019; 8(7) 1596004
[http://dx.doi.org/10.1080/2162402X.2019.1596004] [PMID:  31143517] 
[140] 
Le Page C, Marineau A, Bonza PK, et al. BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PLoS One  2012; 7(6) e38541
[http://dx.doi.org/10.1371/journal.pone.0038541] [PMID:  22685580] 
[141] 
Lan C, Huang X, Lin S, et al. Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat  2013; 12(3): 259-67.
[http://dx.doi.org/10.7785/tcrt.2012.500312] [PMID:  23289476] 
[142] 
Allard B, Longhi MS, Robson SC, Stagg J. The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol Rev  2017; 276(1): 121-44.
[http://dx.doi.org/10.1111/imr.12528] [PMID:  28258700] 
[143] 
Gupta V, Yull F, Khabele D. Bipolar tumor-associated macrophages in ovarian cancer as targets for therapy. Cancers (Basel)  2018; 10(10) E366
[http://dx.doi.org/10.3390/cancers10100366] [PMID:  30274280] 
[144] 
Simeone P, Trerotola M, Franck J, et al. The multiverse nature of epithelial to mesenchymal transition. Semin Cancer Biol 2018.
[PMID: 30453041] 
[145] 
Marchini S, Fruscio R, Clivio L, et al. Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Eur J Cancer  2013; 49(2): 520-30.
[http://dx.doi.org/10.1016/j.ejca.2012.06.026] [PMID:  22897840] 
[146] 
Miow QH, Tan TZ, Ye J, et al. Epithelial-mesenchymal status renders differential responses to cisplatin in ovarian cancer. Oncogene  2015; 34(15): 1899-907.
[http://dx.doi.org/10.1038/onc.2014.136] [PMID:  24858042] 
[147] 
Chebouti I, Kuhlmann JD, Buderath P, et al. ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer. Oncotarget  2017; 8(15): 24303-13.
[http://dx.doi.org/10.18632/oncotarget.13286] [PMID:  28388557] 
[148] 
Veskimäe K, Scaravilli M, Niininen W, et al. Expression analysis of platinum sensitive and resistant epithelial ovarian cancer patient samples reveals new candidates for targeted therapies. Transl Oncol  2018; 11(5): 1160-70.
[http://dx.doi.org/10.1016/j.tranon.2018.07.010] [PMID:  30056367] 
[149] 
van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci  2008; 65(23): 3756-88.
[http://dx.doi.org/10.1007/s00018-008-8281-1] [PMID:  18726070] 
[150] 
Hu QP, Kuang JY, Yang QK, Bian XW, Yu SC. Beyond a tumor suppressor: Soluble E-cadherin promotes the progression of cancer. Int J Cancer  2016; 138(12): 2804-12.
[http://dx.doi.org/10.1002/ijc.29982] [PMID:  26704932] 
[151] 
Rosso M, Majem B, Devis L, et al. E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness. PLoS One  2017; 12(9) e0184439
[http://dx.doi.org/10.1371/journal.pone.0184439] [PMID:  28934230] 
[152] 
Choi PW, Ng SW. The Functions of MicroRNA-200 Family in Ovarian Cancer: Beyond Epithelial-Mesenchymal Transition. Int J Mol Sci  2017; 18(6) E1207
[http://dx.doi.org/10.3390/ijms18061207] [PMID:  28587302] 
[153] 
Zhang B, Wang L, Zhao X, Wei Y, Zhang Y. Identification of Candidate Genes Associated with Chemotherapy Resistance in Ovarian Cancer. Ann Clin Lab Sci  2018; 48(5): 573-9.
[PMID:  30373860] 
[154] 
Abba M, Patil N, Leupold JH, Allgayer H. MicroRNAs-from metastasis prediction to metastasis prevention? Mol Cell Oncol  2015; 3(2) e1074336
[http://dx.doi.org/10.1080/23723556.2015.1074336] [PMID:  27308596] 
[155] 
Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M. Paclitaxel and its evolving role in the management of ovarian cancer. BioMed Res Int  2015; 2015 413076
[http://dx.doi.org/10.1155/2015/413076] [PMID:  26137480] 
[156] 
Norouzi-Barough L, Sarookhani MR, Sharifi M, Moghbelinejad S, Jangjoo S, Salehi R. Molecular mechanisms of drug resistance in ovarian cancer. J Cell Physiol  2018; 233(6): 4546-62.
[http://dx.doi.org/10.1002/jcp.26289] [PMID:  29152737] 
[157] 
Norouzi-Barough L, Sarookhani M, Salehi R, Sharifi M, Moghbelinejad S. CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line. Iran J Basic Med Sci  2018; 21(2): 181-7.
[PMID: 29456815] 
[158] 
Kang YS, Seok HJ, Jeong EJ, et al. DUSP1 induces paclitaxel resistance through the regulation of p-glycoprotein expression in human ovarian cancer cells. Biochem Biophys Res Commun  2016; 478(1): 403-9.
[http://dx.doi.org/10.1016/j.bbrc.2016.07.035] [PMID:  27422607] 
[159] 
Vaidyanathan A, Sawers L, Gannon AL, et al. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. Br J Cancer  2016; 115(4): 431-41.
[http://dx.doi.org/10.1038/bjc.2016.203] [PMID:  27415012] 
[160] 
Johnatty SE, Beesley J, Gao B, et al. ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: a comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas. Gynecol Oncol  2013; 131(1): 8-14.
[http://dx.doi.org/10.1016/j.ygyno.2013.07.107] [PMID:  23917080] 
[161] 
Stordal B, Hamon M, McEneaney V, et al. Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein. PLoS One  2012; 7(7) e40717
[http://dx.doi.org/10.1371/journal.pone.0040717] [PMID:  22792399] 
[162] 
Richardson DL, Sill MW, Coleman RL, et al. Paclitaxel with and without pazopanib for persistent or recurrent ovarian cancer: A Randomized Clinical Trial. JAMA Oncol  2018; 4(2): 196-202.
[http://dx.doi.org/10.1001/jamaoncol.2017.4218] [PMID:  29242937] 
[163] 
Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med  2018; 379(26): 2495-505.
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID:  30345884] 
[164] 
Killock D. Targeted therapy: ARIEL3 - broad benefit of PARP inhibitors in ovarian cancer. Nat Rev Clin Oncol  2017; 14(12): 713.
[http://dx.doi.org/10.1038/nrclinonc.2017.161] [PMID:  28994419] 
[165] 
Del Campo JM, Matulonis UA, Malander S, et al. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol 2019. JCO1802238
[http://dx.doi.org/10.1200/JCO.18.02238] [PMID:  31173551] 
[166] 
Lin KK, Harrell MI, Oza AM, et al. BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma. Cancer Discov  2019; 9(2): 210-9.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0715] [PMID:  30425037] 
[167] 
Gornstein EL, Sandefur S, Chung JH, et al. BRCA2 reversion mutation associated with acquired resistance to olaparib in estrogen receptor-positive breast cancer detected by genomic profiling of tissue and liquid biopsy. Clin Breast Cancer  2018; 18(2): 184-8.
[http://dx.doi.org/10.1016/j.clbc.2017.12.010] [PMID:  29325860] 
[168] 
Domchek SM. Reversion mutations with clinical use of parp inhibitors: many genes, many versions. Cancer Discov  2017; 7(9): 937-9.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0734] [PMID:  28864639] 
[169] 
D’Andrea AD. Mechanisms of PARP inhibitor sensitivity and resistance. DNA Repair (Amst)  2018; 71: 172-6.
[http://dx.doi.org/10.1016/j.dnarep.2018.08.021] [PMID:  30177437] 
[170] 
Stover EH, Konstantinopoulos PA, Matulonis UA, Swisher EM. Biomarkers of response and resistance to dna repair targeted therapies. Clin Cancer Res  2016; 22(23): 5651-60.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0247] [PMID:  27678458] 
[171] 
Mengwasser KE, Adeyemi RO, Leng Y, et al. Genetic screens
reveal fen1 and apex2 as brca2 synthetic lethal targets. Mol Cell  2019; 73(5): 885-99. e886
[http://dx.doi.org/10.1016/j.molcel.2018.12.008] 
[172] 
Le Page C, Wietzerbin J. Modulation of the activation of extracellular signal-regulated kinase (ERK) and the production of inflammatory mediators by ADP-ribosylation inhibitors. Biol Chem  2003; 384(10-11): 1509-13.
[http://dx.doi.org/10.1515/BC.2003.167] [PMID:  14669994] 
[173] 
Huang J, Wang L, Cong Z, et al. The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(-/-) murine model of ovarian cancer. Biochem Biophys Res Commun  2015; 463(4): 551-6.
[http://dx.doi.org/10.1016/j.bbrc.2015.05.083] [PMID:  26047697] 
[174] 
Vinayak S, Tolaney S, Schwartzberg L, et al. Abstract PD5-02: Durability of clinical benefit with niraparib + pembrolizumab in patients with advanced triple-negative breast cancer beyond BRCA: (TOPACIO/Keynote-162). Cancer Research  2019; 79(4 Supplement): PD5-02-PD05-02.
[175] 
Friedlander M, Meniawy T, Markman B, et al. A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors. Journal of Clinical Oncology  2018; 36(5_suppl): 48-8.
[176] 
Spencer KR, Wang J, Silk AW, Ganesan S, Kaufman HL, Mehnert JM. Biomarkers for immunotherapy: current developments and challenges. Am Soc Clin Oncol Educ Book  2016; 35: e493-503.
[http://dx.doi.org/10.1200/EDBK_160766] [PMID:  27249758] 
[177] 
Levinson K, Dorigo O, Rubin K, Moore K. immunotherapy in gynecologic cancers: what we know now and where we are headed. Am Soc Clin Oncol Educ Book  2019; 39: e126-40.
[http://dx.doi.org/10.1200/EDBK_237967] [PMID:  31099679] 
[178] 
Westergaard MCW, Andersen R, Chong C, et al. Tumour-reactive T cell subsets in the microenvironment of ovarian cancer. Br J Cancer  2019; 120(4): 424-34.
[http://dx.doi.org/10.1038/s41416-019-0384-y] [PMID:  30718808] 
[179] 
Fan CA, Reader J, Roque DM. Review of immune therapies targeting ovarian cancer. Curr Treat Options Oncol  2018; 19(12): 74.
[http://dx.doi.org/10.1007/s11864-018-0584-3] [PMID:  30430276] 
[180] 
Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol  2018; 62: 29-39.
[http://dx.doi.org/10.1016/j.intimp.2018.06.001] [PMID:  29990692] 
[181] 
Matulonis UA, Shapira-Frommer R, Santin AD, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol  2019; 30(7): 1080-7.
[http://dx.doi.org/10.1093/annonc/mdz135] [PMID:  31046082] 
[182] 
Disis ML, Taylor MH, Kelly K, et al. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol  2019; 5(3): 393-401.
[http://dx.doi.org/10.1001/jamaoncol.2018.6258] [PMID:  30676622] 
[183] 
Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med  2017; 23(6): 703-13.
[http://dx.doi.org/10.1038/nm.4333] [PMID:  28481359] 
[184] 
Wieser V, Gaugg I, Fleischer M, et al. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer. Oncotarget  2018; 9(25): 17501-11.
[http://dx.doi.org/10.18632/oncotarget.24770] [PMID:  29707124] 
[185] 
Voron T, Colussi O, Marcheteau E, et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med  2015; 212(2): 139-48.
[http://dx.doi.org/10.1084/jem.20140559] [PMID:  25601652] 
[186] 
Rajabi M, Mousa SA. The role of angiogenesis in cancer treatment. Biomedicines  2017; 5(2) E34
[http://dx.doi.org/10.3390/biomedicines5020034] [PMID:  28635679] 
[187] 
Dalton HJ, Fleming ND, Sun CC, Bhosale P, Schmeler KM, Gershenson DM. Activity of bevacizumab-containing regimens in recurrent low-grade serous ovarian or peritoneal cancer: A single institution experience. Gynecol Oncol  2017; 145(1): 37-40.
[http://dx.doi.org/10.1016/j.ygyno.2017.01.027] [PMID:  28139261] 
[188] 
Roviello G, Bachelot T, Hudis CA, et al. The role of bevacizumab in solid tumours: A literature based meta-analysis of randomised trials. Eur J Cancer  2017; 75: 245-58.
[http://dx.doi.org/10.1016/j.ejca.2017.01.026] [PMID:  28242502] 
[189] 
Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol  2014; 32(13): 1302-8.
[http://dx.doi.org/10.1200/JCO.2013.51.4489] [PMID:  24637997] 
[190] 
Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol  2015; 16(8): 928-36.
[http://dx.doi.org/10.1016/S1470-2045(15)00086-8] [PMID:  26115797] 
[191] 
González Martín A, Oza AM, Embleton AC, et al. Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer. Gynecol Oncol  2019; 152(1): 53-60.
[http://dx.doi.org/10.1016/j.ygyno.2018.08.036] [PMID:  30449719] 
[192] 
Lee JY, Park JY, Park SY, et al. Real-world effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA): A Korean Gynecologic Oncology Group study (KGOG 3041). Gynecol Oncol  2019; 152(1): 61-7.
[http://dx.doi.org/10.1016/j.ygyno.2018.10.031] [PMID:  30409490] 
[193] 
Bais C, Mueller B, Brady MF, et al. Tumor microvessel density as a potential predictive marker for bevacizumab benefit: gog-0218 biomarker analyses. J Natl Cancer Inst  2017; 109(11)
[http://dx.doi.org/10.1093/jnci/djx066] [PMID: 29059426] 
[194] 
Han ES, Burger RA, Darcy KM, et al. Predictive and prognostic angiogenic markers in a gynecologic oncology group phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer. Gynecol Oncol  2010; 119(3): 484-90.
[http://dx.doi.org/10.1016/j.ygyno.2010.08.016] [PMID:  20870280] 
[195] 
Collinson F, Hutchinson M, Craven RA, et al. Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection. Clin Cancer Res  2013; 19(18): 5227-39.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0489] [PMID:  23935036] 
[196] 
Collinson F, Hutchinson M, Craven RA, et al. Biomarkers and response to bevacizumab--response. Clin Cancer Res  2014; 20(4): 1058.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3269] [PMID:  24536077] 
[197] 
Backen A, Renehan AG, Clamp AR, et al. The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer. Clin Cancer Res  2014; 20(17): 4549-58.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3248] [PMID:  24947924] 
[198] 
Kommoss S, Winterhoff B, Oberg AL, et al. Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes. Clin Cancer Res  2017; 23(14): 3794-801.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2196] [PMID:  28159814] 
[199] 
Napoletano C, Ruscito I, Bellati F, et al. Bevacizumab-based chemotherapy triggers immunological effects in responding multi-treated recurrent ovarian cancer patients by favoring the recruitment of effector t cell subsets. J Clin Med  2019; 8(3) E380
[http://dx.doi.org/10.3390/jcm8030380] [PMID:  30889935] 
[200] 
Dalton HJ, Pradeep S, McGuire M, et al. Macrophages facilitate resistance to anti-vegf therapy by altered vegfr expression. Clin Cancer Res  2017; 23(22): 7034-46.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0647] [PMID:  28855350] 
[201] 
Lyons YA, Pradeep S, Wu SY, et al. Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy. Oncotarget  2017; 8(57): 96496-505.
[http://dx.doi.org/10.18632/oncotarget.20410] [PMID:  29228548] 
[202] 
Chen YL, Chang MC, Huang CY, et al. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response. Mol Oncol  2012; 6(3): 360-9.
[http://dx.doi.org/10.1016/j.molonc.2011.11.010] [PMID:  22265591] 
[203] 
Kurosaki A, Hasegawa K, Kato T, et al. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression. Int J Cancer  2016; 138(8): 1994-2002.
[http://dx.doi.org/10.1002/ijc.29937] [PMID:  26595060] 
[204] 
Kalli KR, Block MS, Kasi PM, et al. Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients. Clin Cancer Res  2018; 24(13): 3014-25.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2499] [PMID:  29545464] 
[205] 
Ledermann JA, Canevari S, Thigpen T. Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments. Ann Oncol  2015; 26(10): 2034-43.
[http://dx.doi.org/10.1093/annonc/mdv250] [PMID:  26063635] 
[206] 
Reddy JA, Dorton R, Westrick E, et al. Preclinical evaluation of EC145, a folate-vinca alkaloid conjugate. Cancer Res  2007; 67(9): 4434-42.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0033] [PMID:  17483358] 
[207] 
Naumann RW, Coleman RL, Burger RA, et al. PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. J Clin Oncol  2013; 31(35): 4400-6.
[http://dx.doi.org/10.1200/JCO.2013.49.7685] [PMID:  24127448] 
[208] 
Morris RT, Joyrich RN, Naumann RW, et al. Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide). Ann Oncol  2014; 25(4): 852-8.
[http://dx.doi.org/10.1093/annonc/mdu024] [PMID:  24667717] 
[209] 
Guertin AD, O’Neil J, Stoeck A, et al. High Levels of Expression of p-glycoprotein/multidrug resistance protein result in resistance to vintafolide. Mol Cancer Ther  2016; 15(8): 1998-2008.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0950] [PMID:  27256377] 
[210] 
Gershenson DM, Bodurka DC, Coleman RL, Lu KH, Malpica A, Sun CC. Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum. J Clin Oncol  2017; 35(10): 1103-11.
[http://dx.doi.org/10.1200/JCO.2016.71.0632] [PMID:  28221866] 
[211] 
Heinzelmann-Schwarz V, Knipprath Mészaros A, Stadlmann S, et al. Letrozole may be a valuable maintenance treatment in high-grade serous ovarian cancer patients. Gynecol Oncol  2018; 148(1): 79-85.
[http://dx.doi.org/10.1016/j.ygyno.2017.10.036] [PMID:  29157627] 
[212] 
Tang M, O’Connell RL, Amant F, et al. PARAGON: A Phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors. Gynecol Oncol  2019; 154(3): 531-8.
[http://dx.doi.org/10.1016/j.ygyno.2019.06.011] [PMID:  31227223] 
[213] 
Stanley B, Hollis RL, Nunes H, et al. Endocrine treatment of high grade serous ovarian carcinoma; quantification of efficacy and identification of response predictors. Gynecol Oncol  2019; 152(2): 278-85.
[http://dx.doi.org/10.1016/j.ygyno.2018.11.030] [PMID:  30501904] 
[214] 
Huang J, Zhang L, Greshock J, et al. Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome. Genes Chromosomes Cancer  2011; 50(8): 606-18.
[http://dx.doi.org/10.1002/gcc.20883] [PMID:  21563232] 
[215] 
Carden CP, Stewart A, Thavasu P, et al. The association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer. Mol Cancer Ther  2012; 11(7): 1609-17.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0996] [PMID:  22556379] 
[216] 
Cheaib B, Auguste A, Leary A. The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges. Chin J Cancer  2015; 34(1): 4-16.
[http://dx.doi.org/10.5732/cjc.014.10289] [PMID:  25556614] 
[217] 
Gasparri ML, Bardhi E, Ruscito I, et al. PI3K/AKT/mtor pathway in ovarian cancer treatment: are we on the right track? Geburtshilfe Frauenheilkd  2017; 77(10): 1095-103.
[http://dx.doi.org/10.1055/s-0043-118907] [PMID:  29093603] 
[218] 
Wang D, Wang M, Jiang N, et al. Effective use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib to treat PIK3CA mutant ovarian cancer. Oncotarget  2016; 7(11): 13153-66.
[http://dx.doi.org/10.18632/oncotarget.7549] [PMID:  26909613] 
[219] 
Matulonis UA, Wulf GM, Barry WT, et al. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Ann Oncol  2017; 28(3): 512-8.
[PMID: 27993796] 
[220] 
Cheng J, Qin B, Liu B, Huang T, Li Y, Ma L. Maternal embryonic leucine zipper kinase inhibits epithelial-mesenchymal transition by regulating transforming growth factor-β signaling. Oncol Lett  2017; 13(6): 4794-8.
[http://dx.doi.org/10.3892/ol.2017.6081] [PMID:  28588728] 
[221] 
Ganguly R, Hong CS, Smith LG, Kornblum HI, Nakano I. Maternal embryonic leucine zipper kinase: key kinase for stem cell phenotype in glioma and other cancers. Mol Cancer Ther  2014; 13(6): 1393-8.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0764] [PMID:  24795222] 
[222] 
Antony J, Thiery JP, Huang RY. Epithelial-to-mesenchymal transition: lessons from development, insights into cancer and the potential of EMT-subtype based therapeutic intervention. Phys Biol  2019; 16(4) 041004
[http://dx.doi.org/10.1088/1478-3975/ab157a] [PMID:  30939460] 
[223] 
Nussinov R, Tsai CJ, Jang H. Oncogenic Ras Isoforms Signaling Specificity at the Membrane. Cancer Res  2018; 78(3): 593-602.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2727] [PMID:  29273632] 
[224] 
Wong KK, Tsang YT, Deavers MT, et al. BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am J Pathol  2010; 177(4): 1611-7.
[http://dx.doi.org/10.2353/ajpath.2010.100212] [PMID:  20802181] 
[225] 
Farley J, Brady WE, Vathipadiekal V, et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol  2013; 14(2): 134-40.
[http://dx.doi.org/10.1016/S1470-2045(12)70572-7] [PMID:  23261356] 
[226] 
Grisham RN, Moore KN, Gordon MS, et al. Phase ib study of binimetinib with paclitaxel in patients with platinum-resistant ovarian cancer: final results, potential biomarkers, and Extreme Responders. Clin Cancer Res  2018; 24(22): 5525-33.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0494] [PMID:  29844129] 
[227] 
Takekuma M, Wong KK, Coleman RL. A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib. Gynecol Oncol Res Pract  2016; 3: 5.
[http://dx.doi.org/10.1186/s40661-016-0026-5] [PMID:  27231576] 
[228] 
Champer M, Miller D, Kuo DY. Response to trametinib in recurrent low-grade serous ovarian cancer with NRAS mutation: A case report. Gynecol Oncol Rep  2019; 28: 26-8.
[http://dx.doi.org/10.1016/j.gore.2019.01.007] [PMID:  30809568] 
[229] 
Mendivil AA, Tung PK, Bohart R, Bechtol K, Goldstein BH. Dramatic clinical response following dabrafenib and trametinib therapy in a heavily pretreated low grade serous ovarian carcinoma patient with a BRAF V600E mutation. Gynecol Oncol Rep  2018; 26: 41-4.
[http://dx.doi.org/10.1016/j.gore.2018.09.002] [PMID:  30246138] 
[230] 
Bedard PL, Tabernero J, Janku F, et al. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res  2015; 21(4): 730-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1814] [PMID:  25500057] 
[231] 
Garbe C, Eigentler TK. Vemurafenib. Recent Results Cancer Res  2018; 211: 77-89.
[http://dx.doi.org/10.1007/978-3-319-91442-8_6] [PMID:  30069761] 
[232] 
Miller CR, Oliver KE, Farley JH. MEK1/2 inhibitors in the treatment of gynecologic malignancies. Gynecol Oncol  2014; 133(1): 128-37.
[http://dx.doi.org/10.1016/j.ygyno.2014.01.008] [PMID:  24434059] 
[233] 
Spreafico A, Oza AM, Clarke BA, et al. Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC). Gynecol Oncol  2017; 144(2): 250-5.
[http://dx.doi.org/10.1016/j.ygyno.2016.12.002] [PMID:  28062115] 
[234] 
Rodriguez-Freixinos V, Ruiz-Pace F, Fariñas-Madrid L, et al. Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer. ESMO Open  2019; 4(2) e000444
[http://dx.doi.org/10.1136/esmoopen-2018-000444] [PMID:  30962959] 
[235] 
Fernández ML, DiMattia GE, Dawson A, et al. Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines. Am J Cancer Res  2016; 6(10): 2235-51.
[PMID: 27822414] 
[236] 
Fedele C, Ran H, Diskin B, et al. SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models. Cancer Discov  2018; 8(10): 1237-49.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0444] [PMID:  30045908] 
[237] 
Chen SH, Zhang Y, Van Horn RD, et al. Oncogenic braf deletions that function as homodimers and are sensitive to inhibition by raf dimer inhibitor ly3009120. Cancer Discov  2016; 6(3): 300-15.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0896] [PMID:  26732095] 
[238] 
Fernandez ML, Dawson A, Hoenisch J, et al. Markers of MEK inhibitor resistance in low-grade serous ovarian cancer: EGFR is a potential therapeutic target. Cancer Cell Int  2019; 19: 10.
[http://dx.doi.org/10.1186/s12935-019-0725-1] [PMID:  30636931] 
[239] 
Ahmed AA, Etemadmoghadam D, Temple J, et al. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol  2010; 221(1): 49-56.
[http://dx.doi.org/10.1002/path.2696] [PMID:  20229506] 
[240] 
Köbel M, Piskorz AM, Lee S, et al. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res  2016; 2(4): 247-58.
[http://dx.doi.org/10.1002/cjp2.53] [PMID:  27840695] 
[241] 
Lassus H, Butzow R. The classification of p53 immunohistochemical staining results and patient outcome in ovarian cancer. Br J Cancer  2007; 96(10): 1621-2.
[http://dx.doi.org/10.1038/sj.bjc.6603741] [PMID:  17437016] 
[242] 
Bischof K, Knappskog S, Hjelle SM, et al. Influence of p53 isoform expression on survival in high-grade serous ovarian cancers. Sci Rep  2019; 9(1): 5244.
[http://dx.doi.org/10.1038/s41598-019-41706-z] [PMID:  30918304] 
[243] 
Mandilaras V, Garg S, Cabanero M, et al. TP53 mutations in high
grade serous ovarian cancer and impact on clinical outcomes: a
comparison of next generation sequencing and bioinformatics analyses. Int J Gynecol Cancer 2019. ijgc-2018-000087.
[http://dx.doi.org/10.1136/ijgc-2018-000087] [PMID:  30659026] 
[244] 
Sallum LF, Andrade L, Ramalho S, et al. WT1, p53 and p16 expression in the diagnosis of low- and high-grade serous ovarian carcinomas and their relation to prognosis. Oncotarget  2018; 9(22): 15818-27.
[http://dx.doi.org/10.18632/oncotarget.24530] [PMID:  29662608] 
[245] 
Rask L, Høgdall CK, Kjaer SK, et al. Association of cd31 and p53 with survival of ovarian cancer patients. Anticancer Res  2019; 39(2): 567-76.
[http://dx.doi.org/10.21873/anticanres.13149] [PMID:  30711931] 
[246] 
Köbel M, Reuss A, du Bois A, et al. The biological and clinical value of p53 expression in pelvic high-grade serous carcinomas. J Pathol  2010; 222(2): 191-8.
[http://dx.doi.org/10.1002/path.2744] [PMID:  20629008] 
[247] 
Bykov VJ, Issaeva N, Shilov A, et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med  2002; 8(3): 282-8.
[http://dx.doi.org/10.1038/nm0302-282] [PMID:  11875500] 
[248] 
Duffy MJ, Synnott NC, Crown J. Mutant p53 as a target for cancer treatment. Eur J Cancer  2017; 83: 258-65.
[http://dx.doi.org/10.1016/j.ejca.2017.06.023] [PMID:  28756138] 
[249] 
Yu X, Vazquez A, Levine AJ, Carpizo DR. Allele-specific p53 mutant reactivation. Cancer Cell  2012; 21(5): 614-25.
[http://dx.doi.org/10.1016/j.ccr.2012.03.042] [PMID:  22624712] 
[250] 
Mohell N, Alfredsson J, Fransson Å, et al. APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cells. Cell Death Dis  2015; 6 e1794
[http://dx.doi.org/10.1038/cddis.2015.143] [PMID:  26086967] 
[251] 
Fransson Å, Glaessgen D, Alfredsson J, Wiman KG, Bajalica-Lagercrantz S, Mohell N. Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer. J Ovarian Res  2016; 9(1): 27.
[http://dx.doi.org/10.1186/s13048-016-0239-6] [PMID:  27179933] 
[252] 
Gourley C, Green J, Gabra H, et al. PISARRO: A EUTROC phase
Ib study of APR-246 in combination with carboplatin (C) and
pegylated liposomal doxorubicin (PLD) in platinum sensitive relapsed
high grade serous ovarian cancer (HGSOC). Journal of Clinical
Oncology  2016; 34(15_suppl): 5571-1.
[253] 
Macintyre G, Goranova TE, De Silva D, et al. Copy number signatures and mutational processes in ovarian carcinoma. Nat Genet  2018; 50(9): 1262-70.
[http://dx.doi.org/10.1038/s41588-018-0179-8] [PMID:  30104763] 
[254] 
Mayr D, Kanitz V, Anderegg B, et al. Analysis of gene amplification and prognostic markers in ovarian cancer using comparative genomic hybridization for microarrays and immunohistochemical analysis for tissue microarrays. Am J Clin Pathol  2006; 126(1): 101-9.
[http://dx.doi.org/10.1309/N6X5MB24BP42KP20] [PMID:  16753589] 
[255] 
Etemadmoghadam D, deFazio A, Beroukhim R, et al. Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas. Clin Cancer Res  2009; 15(4): 1417-27.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1564] [PMID:  19193619] 
[256] 
Carden CP, Yap TA, Kaye SB. PARP inhibition: targeting the Achilles’ heel of DNA repair to treat germline and sporadic ovarian cancers. Curr Opin Oncol  2010; 22(5): 473-80.
[http://dx.doi.org/10.1097/CCO.0b013e32833b5126] [PMID:  20485165] 
[257] 
Etemadmoghadam D, Weir BA, Au-Yeung G, et al. Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proc Natl Acad Sci USA  2013; 110(48): 19489-94.
[http://dx.doi.org/10.1073/pnas.1314302110] [PMID:  24218601] 
[258] 
Gunn S, Reveles X, Weldon K, et al. Molecular cytogenetics as a clinical test for prognostic and predictive biomarkers in newly diagnosed ovarian cancer. J Ovarian Res  2013; 6(1): 2.
[http://dx.doi.org/10.1186/1757-2215-6-2] [PMID:  23289505] 
[259] 
da Costa AABA, do Canto LM, Larsen SJ, et al. Genomic profiling in ovarian cancer retreated with platinum based chemotherapy presented homologous recombination deficiency and copy number imbalances of CCNE1 and RB1 genes. BMC Cancer  2019; 19(1): 422.
[http://dx.doi.org/10.1186/s12885-019-5622-4] [PMID:  31060523] 
[260] 
Lu X, Lu J, Liao B, Li X, Qian X, Li K. Driver pattern identification over the gene co-expression of drug response in ovarian cancer by integrating high throughput genomics data. Sci Rep  2017; 7(1): 16188.
[http://dx.doi.org/10.1038/s41598-017-16286-5] [PMID:  29170526] 
[261] 
Niazi MKK, Parwani AV, Gurcan MN. Digital pathology and artificial intelligence. Lancet Oncol  2019; 20(5): e253-61.
[http://dx.doi.org/10.1016/S1470-2045(19)30154-8] [PMID:  31044723] 
[262] 
Heindl A, Khan AM, Rodrigues DN, et al. Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity. Nat Commun  2018; 9(1): 3917.
[http://dx.doi.org/10.1038/s41467-018-06130-3] [PMID:  30254278] 
[263] 
Gasparri ML, Savone D, Besharat RA, et al. Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer. Tumour Biol  2016; 37(1): 71-5.
[http://dx.doi.org/10.1007/s13277-015-4299-9] [PMID:  26500096] 
[264] 
Rubatt JM, Darcy KM, Tian C, et al. Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study. Gynecol Oncol  2012; 125(2): 421-6.
[http://dx.doi.org/10.1016/j.ygyno.2012.01.008] [PMID:  22261301] 
[265] 
Kamat AA, Bischoff FZ, Dang D, et al. Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer Biol Ther  2006; 5(10): 1369-74.
[http://dx.doi.org/10.4161/cbt.5.10.3240] [PMID:  16969071] 
[266] 
Capizzi E, Gabusi E, Grigioni AD, et al. Quantification of free plasma DNA before and after chemotherapy in patients with advanced epithelial ovarian cancer. Diagn Mol Pathol  2008; 17(1): 34-8.
[http://dx.doi.org/10.1097/PDM.0b013e3181359e1f] [PMID:  18303408] 
[267] 
Dobrzycka B, Terlikowski SJ, Kinalski M, Kowalczuk O, Niklinska W, Chyczewski L. Circulating free DNA and p53 antibodies in plasma of patients with ovarian epithelial cancers. Ann Oncol  2011; 22(5): 1133-40.
[http://dx.doi.org/10.1093/annonc/mdq584] [PMID:  21098618] 
[268] 
Steffensen KD, Madsen CV, Andersen RF, Waldstrøm M, Adimi P, Jakobsen A. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab. Eur J Cancer  2014; 50(15): 2611-8.
[http://dx.doi.org/10.1016/j.ejca.2014.06.022] [PMID:  25087181] 
[269] 
Slavin TP, Banks KC, Chudova D, et al. Identification of incidental germline mutations in patients with advanced solid tumors who underwent cell-free circulating tumor dna sequencing. J Clin Oncol 2018. JCO1800328
[http://dx.doi.org/10.1200/JCO.18.00328] [PMID:  30339520] 
[270] 
Barbosa A, Peixoto A, Pinto P, Pinheiro M, Teixeira MR. Potential clinical applications of circulating cell-free DNA in ovarian cancer patients. Expert Rev Mol Med  2018; 20e6
[http://dx.doi.org/10.1017/erm.2018.5] [PMID:  30558693] 
[271] 
Deans ZC, Williams H, Dequeker EMC, et al. IQN Path ASBL. Review of the implementation of plasma ctDNA testing on behalf of IQN Path ASBL: a perspective from an EQA providers’ survey. Virchows Arch  2017; 471(6): 809-13.
[http://dx.doi.org/10.1007/s00428-017-2222-z] [PMID:  28840321] 
[272] 
Swisher EM, Wollan M, Mahtani SM, et al. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am J Obstet Gynecol  2005; 193(3 Pt 1): 662-7.
[http://dx.doi.org/10.1016/j.ajog.2005.01.054] [PMID:  16150257] 
[273] 
Lebofsky R, Decraene C, Bernard V, et al. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types. Mol Oncol  2015; 9(4): 783-90.
[http://dx.doi.org/10.1016/j.molonc.2014.12.003] [PMID:  25579085] 
[274] 
Mari R, Mamessier E, Lambaudie E, et al. Liquid Biopsies for Ovarian Carcinoma: How Blood Tests May Improve the Clinical Management of a Deadly Disease. Cancers (Basel)  2019; 11(6) E774
[http://dx.doi.org/10.3390/cancers11060774] [PMID:  31167492] 
[275] 
Pereira E, Camacho-Vanegas O, Anand S, et al. Personalized circulating tumor dna biomarkers dynamically predict treatment response and survival in gynecologic cancers. PLoS One  2015; 10(12) e0145754
[http://dx.doi.org/10.1371/journal.pone.0145754] [PMID:  26717006] 
[276] 
Parkinson CA, Gale D, Piskorz AM, et al. Exploratory analysis of tp53 mutations in circulating tumour dna as biomarkers of treatment response for patients with relapsed high-grade serous ovarian carcinoma: a retrospective study. PLoS Med  2016; 13(12) e1002198
[http://dx.doi.org/10.1371/journal.pmed.1002198] [PMID:  27997533] 
[277] 
Martignetti JA, Camacho-Vanegas O, Priedigkeit N, et al. Personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor DNA. Neoplasia  2014; 16(1): 97-103.
[http://dx.doi.org/10.1593/neo.131900] [PMID:  24563622] 
[278] 
Weigelt B, Comino-Méndez I, de Bruijn I, et al. Diverse brca1 and brca2 reversion mutations in circulating cell-free dna of therapy-resistant breast or ovarian cancer. Clin Cancer Res  2017; 23(21): 6708-20.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0544] [PMID:  28765325] 
[279] 
Quigley D, Alumkal JJ, Wyatt AW, et al. Analysis of circulating cell-free dna identifies multiclonal heterogeneity of brca2 reversion mutations associated with resistance to parp inhibitors. Cancer Discov  2017; 7(9): 999-1005.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0146] [PMID:  28450426] 
[280] 
Shi M, Mu Y, Zhang H, et al. MicroRNA-200 and microRNA-30 family as prognostic molecular signatures in ovarian cancer: A meta-analysis. Medicine (Baltimore)  2018; 97(32) e11505
[http://dx.doi.org/10.1097/MD.0000000000011505] [PMID:  30095616] 
[281] 
Giannopoulou L, Zavridou M, Kasimir-Bauer S, Lianidou ES. Liquid biopsy in ovarian cancer: the potential of circulating miRNAs and exosomes. Transl Res  2019; 205: 77-91.
[http://dx.doi.org/10.1016/j.trsl.2018.10.003] [PMID:  30391474] 
[282] 
Wang X, Kong D, Wang C, et al. Circulating microRNAs as novel potential diagnostic biomarkers for ovarian cancer: a systematic review and updated meta-analysis. J Ovarian Res  2019; 12(1): 24.
[http://dx.doi.org/10.1186/s13048-019-0482-8] [PMID:  30898156] 
[283] 
Kapetanakis NI, Uzan C, Jimenez-Pailhes AS, et al. Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival. Oncotarget  2015; 6(34): 36815-24.
[http://dx.doi.org/10.18632/oncotarget.5766] [PMID:  26416421] 
[284] 
Shi C, Zhang Z. The prognostic value of the miR-200 family in ovarian cancer: a meta-analysis. Acta Obstet Gynecol Scand  2016; 95(5): 505-12.
[http://dx.doi.org/10.1111/aogs.12883] [PMID:  26910180] 
[285] 
Meng X, Müller V, Milde-Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Oncotarget  2016; 7(13): 16923-35.
[http://dx.doi.org/10.18632/oncotarget.7850] [PMID:  26943577] 
[286] 
Halvorsen AR, Kristensen G, Embleton A, et al. Evaluation of prognostic and predictive significance of circulating micrornas in ovarian cancer patients. Dis Markers  2017; 2017 3098542
[http://dx.doi.org/10.1155/2017/3098542] [PMID:  28293063] 
[287] 
Bagnoli M, Canevari S, Califano D, et al. Development and validation of a microRNA-based signature (MiROvaR) to predict early relapse or progression of epithelial ovarian cancer: a cohort study. Lancet Oncol  2016; 17(8): 1137-46.
[http://dx.doi.org/10.1016/S1470-2045(16)30108-5] [PMID:  27402147] 
[288] 
Cramer DW, Elias KM. A prognostically relevant miRNA signature for epithelial ovarian cancer. Lancet Oncol  2016; 17(8): 1032-3.
[http://dx.doi.org/10.1016/S1470-2045(16)30149-8] [PMID:  27402146] 
[289] 
Panebianco C, Andriulli A, Pazienza V. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. Microbiome  2018; 6(1): 92.
[http://dx.doi.org/10.1186/s40168-018-0483-7] [PMID:  29789015] 
[290] 
Vernocchi P, Del Chierico F, Putignani L. Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health. Front Microbiol  2016; 7: 1144.
[http://dx.doi.org/10.3389/fmicb.2016.01144] [PMID:  27507964] 
[291] 
Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med  2019; 25(3): 377-88.
[http://dx.doi.org/10.1038/s41591-019-0377-7] [PMID:  30842679] 
[292] 
Zhou B, Sun C, Huang J, et al. The biodiversity Composition of Microbiome in Ovarian Carcinoma Patients. Sci Rep  2019; 9(1): 1691.
[http://dx.doi.org/10.1038/s41598-018-38031-2] [PMID:  30737418] 
[293] 
Hoppenot C, Eckert MA, Tienda SM, Lengyel E. Who are the long-term survivors of high grade serous ovarian cancer? Gynecol Oncol  2018; 148(1): 204-12.
[http://dx.doi.org/10.1016/j.ygyno.2017.10.032] [PMID:  29128106] 
[294] 
Le Saux O, Decullier E, Freyer G, Glehen O, Bakrin N. Long-term survival in patients with epithelial ovarian cancer following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Int J Hyperthermia  2018; 35(1): 652-7.
[http://dx.doi.org/10.1080/02656736.2018.1518544] [PMID:  30295114] 
[295] 
Dao F, Schlappe BA, Tseng J, et al. Characteristics of 10-year survivors of high-grade serous ovarian carcinoma. Gynecol Oncol  2016; 141(2): 260-3.
[http://dx.doi.org/10.1016/j.ygyno.2016.03.010] [PMID:  26968641] 
[296] 
Cress RD, Chen YS, Morris CR, Petersen M, Leiserowitz GS. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer. Obstet Gynecol  2015; 126(3): 491-7.
[http://dx.doi.org/10.1097/AOG.0000000000000981] [PMID:  26244529] 
[297] 
Chang SJ, Bristow RE. Evolution of surgical treatment paradigms for advanced-stage ovarian cancer: redefining ‘optimal’ residual disease. Gynecol Oncol  2012; 125(2): 483-92.
[http://dx.doi.org/10.1016/j.ygyno.2012.02.024] [PMID:  22366151] 
[298] 
Bookman MA, Okamoto A, Stuart G, et al. Harmonising clinical
trials within the Gynecologic Cancer InterGroup: consensus and
unmet needs from the Fifth Ovarian Cancer Consensus Conference. Ann Oncol  2017; 28(suppl_8): viii30-5.
[299] 
Yang SYC, Lheureux S, Karakasis K, et al. Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors. Genome Med  2018; 10(1): 81.
[http://dx.doi.org/10.1186/s13073-018-0590-x] [PMID:  30382883] 
[300] 
Kotsopoulos J, Rosen B, Fan I, et al. Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status. Gynecol Oncol  2016; 140(1): 42-7.
[http://dx.doi.org/10.1016/j.ygyno.2015.11.009] [PMID:  26556769] 
[301] 
Safra T, Lai WC, Borgato L, et al. BRCA mutations and outcome
in epithelial ovarian cancer (EOC): experience in ethnically diverse
groups. Ann Oncol 2013  2013; 24  Suppl: viii63-viii68
[302] 
Rytelewski M, Tong JG, Buensuceso A, et al. BRCA2 inhibition enhances cisplatin-mediated alterations in tumor cell proliferation, metabolism, and metastasis. Mol Oncol  2014; 8(8): 1429-40.
[http://dx.doi.org/10.1016/j.molonc.2014.05.017] [PMID:  24974076] 
[303] 
Quinn JE, James CR, Stewart GE, et al. BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy. Clin Cancer Res  2007; 13(24): 7413-20.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1083] [PMID:  18094425] 
[304] 
Lheureux S, Lai Z, Dougherty BA, et al. Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: clinical and molecular characterization. Clin Cancer Res  2017; 23(15): 4086-94.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2615] [PMID:  28223274] 
[305] 
Norquist BM, Harrell MI, Brady MF, et al. Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol  2016; 2(4): 482-90.
[http://dx.doi.org/10.1001/jamaoncol.2015.5495] [PMID:  26720728] 
[306] 
Darb-Esfahani S, Kolaschinski I, Trillsch F, et al. Morphology and tumour-infiltrating lymphocytes in high-stage, high-grade serous ovarian carcinoma correlated with long-term survival. Histopathology  2018; 73(6): 1002-12.
[http://dx.doi.org/10.1111/his.13711] [PMID:  30007074] 
[307] 
Abed MN, Abdullah MI, Richardson A. Antagonism of Bcl-XL is necessary for synergy between carboplatin and BH3 mimetics in ovarian cancer cells. J Ovarian Res  2016; 9: 25.
[http://dx.doi.org/10.1186/s13048-016-0234-y] [PMID:  27080533] 
[308] 
Fleury H, Malaquin N, Tu V, et al. Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence. Nat Commun  2019; 10(1): 2556.
[http://dx.doi.org/10.1038/s41467-019-10460-1] [PMID:  31186408] 
[309] 
Zervantonakis IK, Iavarone C, Chen HY, et al. Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response. Nat Commun  2017; 8(1): 365.
[http://dx.doi.org/10.1038/s41467-017-00263-7] [PMID:  28848242] 
[310] 
Konecny GE. Cyclin-dependent kinase pathways as targets for women’s cancer treatment. Curr Opin Obstet Gynecol  2016; 28(1): 42-8.
[http://dx.doi.org/10.1097/GCO.0000000000000243] [PMID:  26642065] 
[311] 
Rambau PF, Vierkant RA, Intermaggio MP, et al. AOCS Group. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an ovarian tumor tissue analysis consortium study. J Pathol Clin Res  2018; 4(4): 250-61.
[http://dx.doi.org/10.1002/cjp2.109] [PMID:  30062862] 
[312] 
Yang ZM, Liao XM, Chen Y, et al. Combining 53BP1 with BRCA1 as a biomarker to predict the sensitivity of poly(ADP-ribose) polymerase (PARP) inhibitors. Acta Pharmacol Sin  2017; 38(7): 1038-47.
[http://dx.doi.org/10.1038/aps.2017.8] [PMID:  28414200] 
[313] 
Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med  2015; 373(8): 726-36.
[http://dx.doi.org/10.1056/NEJMoa1502309] [PMID:  26287849] 
[314] 
Turcotte M, Spring K, Pommey S, et al. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res  2015; 75(21): 4494-503.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3569] [PMID:  26363007] 
[315] 
Konecny GE, Winterhoff B, Kolarova T, et al. Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res  2011; 17(6): 1591-602.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2307] [PMID:  21278246] 
[316] 
Song H, Dicks E, Ramus SJ, et al. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. J Clin Oncol  2015; 33(26): 2901-7.
[http://dx.doi.org/10.1200/JCO.2015.61.2408] [PMID:  26261251] 
Rights & Permissions Print Cite
Article Metrics
20
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1389450120666191016143836	Print ISSN 1389-4501
Publisher Name Bentham Science Publisher	Online ISSN 1873-5592
当代药物靶点

探讨预测生物标志物对浆液性卵巢癌的临床影响

摘要

图形摘要

当代药物靶点

探讨预测生物标志物对浆液性卵巢癌的临床影响

摘要 Play Pause

图形摘要

Related Journals

Related Books

Related Articles

摘要
