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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

Strategic Combination Therapies for Ovarian Cancer

Author(s): Xinran Li, Angel S.N. Ng, Victor C.Y. Mak, Karen K.L. Chan, Annie N.Y. Cheung and Lydia W.T. Cheung*

Volume 20, Issue 8, 2020

Page: [573 - 585] Pages: 13

DOI: 10.2174/1568009620666200511084007

Price: $65

Abstract

Ovarian cancer remains the leading cause of gynecologic cancer-related deaths among women worldwide. The dismal survival rate is partially due to recurrence after standardized debulking surgery and first-line chemotherapy. In recent years, targeted therapies, including antiangiogenic agents or poly (ADP-ribose) polymerase inhibitors, represent breakthroughs in the treatment of ovarian cancer. As more therapeutic agents become available supplemented by a deeper understanding of ovarian cancer biology, a range of combination treatment approaches are being actively investigated to further improve the clinical outcomes of the disease. These combinations, which involve DNA-damaging agents, targeted therapies of signaling pathways and immunotherapies, simultaneously target multiple cancer pathways or hallmarks to induce additive or synergistic antitumor activities. Here we review the preclinical data and ongoing clinical trials for developing effective combination therapies in treating ovarian cancer. These emerging therapeutic modalities may reshape the treatment landscape of the disease.

Keywords: Chemotherapy, combination treatment, immunotherapy, ovarian cancer, targeted therapy, poly (ADP-ribose) polymerase inhibitors.

« Previous Next »
[1]
Ahmed, F.Y.; Wiltshaw, E.; A’Hern, R.P.; Nicol, B.; Shepherd, J.; Blake, P.; Fisher, C.; Gore, M.E. Natural history and prognosis of untreated stage I epithelial ovarian carcinoma. J. Clin. Oncol., 1996, 14(11), 2968-2975.
[http://dx.doi.org/10.1200/JCO.1996.14.11.2968] [PMID: 8918494]
[2]
Buys, S.S.; Partridge, E.; Black, A.; Johnson, C.C.; Lamerato, L.; Isaacs, C.; Reding, D.J.; Greenlee, R.T.; Yokochi, L.A.; Kessel, B.; Crawford, E.D.; Church, T.R.; Andriole, G.L.; Weissfeld, J.L.; Fouad, M.N.; Chia, D.; O’Brien, B.; Ragard, L.R.; Clapp, J.D.; Rathmell, J.M.; Riley, T.L.; Hartge, P.; Pinsky, P.F.; Zhu, C.S.; Izmirlian, G.; Kramer, B.S.; Miller, A.B.; Xu, J.L.; Prorok, P.C.; Gohagan, J.K.; Berg, C.D. PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA, 2011, 305(22), 2295-2303.
[http://dx.doi.org/10.1001/jama.2011.766] [PMID: 21642681]
[3]
Gershenson, D.M.; Wharton, J.T.; Copeland, L.J.; Stringer, C.A.; Edwards, C.L.; Kavanagh, J.J.; Freedman, R.S. Treatment of advanced epithelial ovarian cancer with cisplatin and cyclophosphamide. Gynecol. Oncol., 1989, 32(3), 336-341.
[http://dx.doi.org/10.1016/0090-8258(89)90636-7] [PMID: 2920954]
[4]
McGuire, W.P.; Hoskins, W.J.; Brady, M.F.; Kucera, P.R.; Partridge, E.E.; Look, K.Y.; Clarke-Pearson, D.L.; Davidson, M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N. Engl. J. Med., 1996, 334(1), 1-6.
[http://dx.doi.org/10.1056/NEJM199601043340101] [PMID: 7494563]
[5]
du Bois, A.; Lück, H.J.; Meier, W.; Adams, H.P.; Möbus, V.; Costa, S.; Bauknecht, T.; Richter, B.; Warm, M.; Schröder, W.; Olbricht, S.; Nitz, U.; Jackisch, C.; Emons, G.; Wagner, U.; Kuhn, W.; Pfisterer, J. Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J. Natl. Cancer Inst., 2003, 95(17), 1320-1329.
[http://dx.doi.org/10.1093/jnci/djg036] [PMID: 12953086]
[6]
Yang, J.; Nie, J.; Ma, X.; Wei, Y.; Peng, Y.; Wei, X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol. Cancer, 2019, 18(1), 26.
[http://dx.doi.org/10.1186/s12943-019-0954-x] [PMID: 30782187]
[7]
Damia, G.; Broggini, M. Platinum resistance in ovarian cancer: Role of DNA repair. Cancers (Basel), 2019, 11(1), 11.
[http://dx.doi.org/10.3390/cancers11010119] [PMID: 30669514]
[8]
Oda, K.; Hamanishi, J.; Matsuo, K.; Hasegawa, K. Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management. Gynecol. Oncol., 2018, 151(2), 381-389.
[http://dx.doi.org/10.1016/j.ygyno.2018.09.001] [PMID: 30217369]
[9]
Farmer, H.; McCabe, N.; Lord, C.J.; Tutt, A.N.; Johnson, D.A.; Richardson, T.B.; Santarosa, M.; Dillon, K.J.; Hickson, I.; Knights, C.; Martin, N.M.; Jackson, S.P.; Smith, G.C.; Ashworth, A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005, 434(7035), 917-921.
[http://dx.doi.org/10.1038/nature03445] [PMID: 15829967]
[10]
Shah, M.A.; Schwartz, G.K. Cell cycle-mediated drug resistance: An emerging concept in cancer therapy. Clin. Cancer Res., 2001, 7(8), 2168-2181.
[PMID: 11489790]
[11]
Huehls, A.M.; Wagner, J.M.; Huntoon, C.J.; Karnitz, L.M. Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination. Mol. Pharmacol., 2012, 82(4), 767-776.
[http://dx.doi.org/10.1124/mol.112.080614] [PMID: 22833573]
[12]
Clark, C.C.; Weitzel, J.N.; O’Connor, T.R. Enhancement of synthetic lethality via combinations of ABT-888, a PARP inhibitor, and carboplatin in vitro and in vivo using BRCA1 and BRCA2 isogenic models. Mol. Cancer Ther., 2012, 11(9), 1948-1958.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0597] [PMID: 22778154]
[13]
Oza, A.M.; Cibula, D.; Benzaquen, A.O.; Poole, C.; Mathijssen, R.H.; Sonke, G.S.; Colombo, N.; Špaček, J.; Vuylsteke, P.; Hirte, H.; Mahner, S.; Plante, M.; Schmalfeldt, B.; Mackay, H.; Rowbottom, J.; Lowe, E.S.; Dougherty, B.; Barrett, J.C.; Friedlander, M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: A randomised phase 2 trial. Lancet Oncol., 2015, 16(1), 87-97.
[http://dx.doi.org/10.1016/S1470-2045(14)71135-0] [PMID: 25481791]
[14]
Del Conte, G.; Sessa, C.; von Moos, R.; Viganò, L.; Digena, T.; Locatelli, A.; Gallerani, E.; Fasolo, A.; Tessari, A.; Cathomas, R.; Gianni, L. Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. Br. J. Cancer, 2014, 111(4), 651-659.
[http://dx.doi.org/10.1038/bjc.2014.345] [PMID: 25025963]
[15]
Gray, H.J.; Bell-McGuinn, K.; Fleming, G.F.; Cristea, M.; Xiong, H.; Sullivan, D.; Luo, Y.; McKee, M.D.; Munasinghe, W.; Martin, L.P. Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies. Gynecol. Oncol., 2018, 148(3), 507-514.
[http://dx.doi.org/10.1016/j.ygyno.2017.12.029] [PMID: 29352572]
[16]
Kramer, D.; Stark, N.; Schulz-Heddergott, R.; Erytch, N.; Edmunds, S.; Roßmann, L.; Bastians, H.; Concin, N.; Moll, U.M.; Dobbelstein, M. Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells. Cell Death Differ., 2017, 24(2), 300-316.
[http://dx.doi.org/10.1038/cdd.2016.124] [PMID: 27834954]
[17]
Kim, H.; George, E.; Ragland, R.; Rafail, S.; Zhang, R.; Krepler, C.; Morgan, M.; Herlyn, M.; Brown, E.; Simpkins, F. Targeting the ATR/CHK1 axis with PARP inhibition results in tumor regression in BRCA-mutant ovarian cancer models. Clin. Cancer Res., 2017, 23(12), 3097-3108.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2273] [PMID: 27993965]
[18]
Meng, X.; Bi, J.; Li, Y.; Yang, S.; Zhang, Y.; Li, M.; Liu, H.; Li, Y.; Mcdonald, M.E.; Thiel, K.W.; Wen, K.K.; Wang, X.; Wu, M.; Leslie, K.K. AZD1775 increases sensitivity to olaparib and gemcitabine in cancer cells with p53 mutations. Cancers (Basel), 2018, 10(5), 149.
[http://dx.doi.org/10.3390/cancers10050149] [PMID: 29783721]
[19]
Leijen, S.; van Geel, R.M.; Sonke, G.S.; de Jong, D.; Rosenberg, E.H.; Marchetti, S.; Pluim, D.; van Werkhoven, E.; Rose, S.; Lee, M.A.; Freshwater, T.; Beijnen, J.H.; Schellens, J.H. Phase II study of WEE1 inhibitor AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months. J. Clin. Oncol., 2016, 34(36), 4354-4361.
[http://dx.doi.org/10.1200/JCO.2016.67.5942] [PMID: 27998224]
[20]
Fang, Y.; McGrail, D.J.; Sun, C.; Labrie, M.; Chen, X.; Zhang, D. Sequential therapy with PARP and WEE1 inhibitors minimizes toxicity while maintaining efficacy. Cancer Cell, 2019, 35, 851-867.
[http://dx.doi.org/10.1016/j.ccell.2019.05.001]
[21]
Karakashev, S.; Zhu, H.; Yokoyama, Y.; Zhao, B.; Fatkhutdinov, N.; Kossenkov, A.V.; Wilson, A.J.; Simpkins, F.; Speicher, D.; Khabele, D.; Bitler, B.G.; Zhang, R. BET bromodomain inhibition synergizes with PARP inhibitor in epithelial ovarian cancer. Cell Rep., 2017, 21(12), 3398-3405.
[http://dx.doi.org/10.1016/j.celrep.2017.11.095] [PMID: 29262321]
[22]
Yokoyama, T.; Kohn, E.C.; Brill, E.; Lee, J.M. Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2/Bcl-xL and PARP. Int. J. Oncol., 2017, 50, 1064-1074.
[http://dx.doi.org/10.3892/ijo.2017.3914] [PMID: 28350129]
[23]
Song, T.; Zhang, M.; Liu, P.; Xue, Z.; Fan, Y.; Zhang, Z. Identification of JNK1 as a predicting biomarker for ABT-199 and paclitaxel combination treatment. Biochem. Pharmacol., 2018, 155, 102-109.
[http://dx.doi.org/10.1016/j.bcp.2018.06.019] [PMID: 29953843]
[24]
Fransson, Å.; Glaessgen, D.; Alfredsson, J.; Wiman, K.G.; 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]
[25]
Aghajanian, C.; Blank, S.V.; Goff, B.A.; Judson, P.L.; Teneriello, M.G.; Husain, A.; Sovak, M.A.; Yi, J.; Nycum, L.R. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J. Clin. Oncol., 2012, 30(17), 2039-2045.
[http://dx.doi.org/10.1200/JCO.2012.42.0505] [PMID: 22529265]
[26]
Pujade-Lauraine, E.; Hilpert, F.; Weber, B.; Reuss, A.; Poveda, A.; Kristensen, G.; Sorio, R.; Vergote, I.; Witteveen, P.; Bamias, A.; Pereira, D.; Wimberger, P.; Oaknin, A.; Mirza, M.R.; Follana, P.; Bollag, D.; Ray-Coquard, I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J. Clin. Oncol., 2014, 32(13), 1302-1308.
[http://dx.doi.org/10.1200/JCO.2013.51.4489] [PMID: 24637997]
[27]
Fleming, N.D.; Coleman, R.L.; Tung, C.; Westin, S.N.; Hu, W.; Sun, Y.; Bhosale, P.; Munsell, M.F.; Sood, A.K. Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer. Gynecol. Oncol., 2017, 147(1), 41-46.
[http://dx.doi.org/10.1016/j.ygyno.2017.07.137] [PMID: 28774461]
[28]
Liu, J.F.; Barry, W.T.; Birrer, M.; Lee, J.M.; Buckanovich, R.J.; Fleming, G.F.; Rimel, B.J.; Buss, M.K.; Nattam, S.R.; Hurteau, J.; Luo, W.; Curtis, J.; Whalen, C.; Kohn, E.C.; Ivy, S.P.; Matulonis, U.A. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann. Oncol., 2019, 30(4), 551-557.
[http://dx.doi.org/10.1093/annonc/mdz018] [PMID: 30753272]
[29]
Kaplan, A.R.; Gueble, S.E.; Liu, Y.; Oeck, S.; Kim, H.; Yun, Z.; Glazer, P.M. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Sci. Transl. Med., 2019, 11(492)eaav4508
[http://dx.doi.org/10.1126/scitranslmed.aav4508] [PMID: 31092693]
[30]
Ray-Coquard, I.; Pautier, P.; Pignata, S.; Pérol, D.; González-Martín, A.; Berger, R.; Fujiwara, K.; Vergote, I.; Colombo, N.; Mäenpää, J.; Selle, F.; Sehouli, J.; Lorusso, D.; Guerra Alía, E.M.; Reinthaller, A.; Nagao, S.; Lefeuvre-Plesse, C.; Canzler, U.; Scambia, G.; Lortholary, A.; Marmé, F.; Combe, P.; de Gregorio, N.; Rodrigues, M.; Buderath, P.; Dubot, C.; Burges, A.; You, B.; Pujade-Lauraine, E.; Harter, P. PAOLA-1 Investigators Olaparib plus Bevacizumab as first-line maintenance in ovarian cancer. N. Engl. J. Med., 2019, 381(25), 2416-2428.
[http://dx.doi.org/10.1056/NEJMoa1911361] [PMID: 31851799]
[31]
Sheng, Q.; Liu, J. The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer. Br. J. Cancer, 2011, 104(8), 1241-1245.
[http://dx.doi.org/10.1038/bjc.2011.62] [PMID: 21364581]
[32]
Blank, S.V.; Christos, P.; Curtin, J.P.; Goldman, N.; Runowicz, C.D.; Sparano, J.A.; Liebes, L.; Chen, H.X.; Muggia, F.M. Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: a phase II study based on surgical reassessment. Gynecol. Oncol., 2010, 119(3), 451-456.
[http://dx.doi.org/10.1016/j.ygyno.2010.08.008] [PMID: 20837357]
[33]
Secord, A.A.; Blessing, J.A.; Armstrong, D.K.; Rodgers, W.H.; Miner, Z.; Barnes, M.N.; Lewandowski, G.; Mannel, R.S. Gynecologic Oncology Group Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study. Gynecol. Oncol., 2008, 108(3), 493-499.
[http://dx.doi.org/10.1016/j.ygyno.2007.11.029] [PMID: 18191993]
[34]
Nimeiri, H.S.; Oza, A.M.; Morgan, R.J.; Friberg, G.; Kasza, K.; Faoro, L.; Salgia, R.; Stadler, W.M.; Vokes, E.E.; Fleming, G.F. Chicago Phase II Consortium; PMH Phase II Consortium; California Phase II Consortium. Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: A trial of the Chicago, PMH, and California Phase II Consortia. Gynecol. Oncol., 2008, 110(1), 49-55.
[http://dx.doi.org/10.1016/j.ygyno.2008.02.009] [PMID: 18423560]
[35]
Coleman, R.L.; Moon, J.; Sood, A.K.; Hu, W.; Delmore, J.E.; Bonebrake, A.J.; Anderson, G.L.; Chambers, S.K.; Markman, M. Randomised phase II study of docetaxel plus vandetanib versus docetaxel followed by vandetanib in patients with persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: SWOG S0904. Eur. J. Cancer, 2014, 50(9), 1638-1648.
[http://dx.doi.org/10.1016/j.ejca.2014.03.005] [PMID: 24709487]
[36]
Lheureux, S.; Krieger, S.; Weber, B.; Pautier, P.; Fabbro, M.; Selle, F.; Bourgeois, H.; Petit, T.; Lortholary, A.; Plantade, A.; Briand, M.; Leconte, A.; Richard, N.; Vilquin, P.; Clarisse, B.; Blanc-Fournier, C.; Joly, F. Expected benefits of topotecan combined with lapatinib in recurrent ovarian cancer according to biological profile: a phase 2 trial. Int. J. Gynecol. Cancer, 2012, 22(9), 1483-1488.
[http://dx.doi.org/10.1097/IGC.0b013e31826d1438] [PMID: 23027040]
[37]
Sui, H.; Shi, C.; Yan, Z.; Li, H. Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy. Drug Des. Devel. Ther., 2015, 9, 3183-3190.
[http://dx.doi.org/10.2147/DDDT.S82035] [PMID: 26124641]
[38]
Makhija, S.; Amler, L.C.; Glenn, D.; Ueland, F.R.; Gold, M.A.; Dizon, D.S.; Paton, V.; Lin, C.Y.; Januario, T.; Ng, K.; Strauss, A.; Kelsey, S.; Sliwkowski, M.X.; Matulonis, U. Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J. Clin. Oncol., 2010, 28(7), 1215-1223.
[http://dx.doi.org/10.1200/JCO.2009.22.3354] [PMID: 19901115]
[39]
Kurzeder, C.; Bover, I.; Marmé, F.; Rau, J.; Pautier, P.; Colombo, N.; Lorusso, D.; Ottevanger, P.; Bjurberg, M.; Marth, C.; Barretina-Ginesta, P.; Vergote, I.; Floquet, A.; Del Campo, J.M.; Mahner, S.; Bastière-Truchot, L.; Martin, N.; Oestergaard, M.Z.; Kiermaier, A.; Schade-Brittinger, C.; Polleis, S.; du Bois, A.; Gonzalez-Martin, A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J. Clin. Oncol., 2016, 34(21), 2516-2525.
[http://dx.doi.org/10.1200/JCO.2015.66.0787] [PMID: 27269942]
[40]
Kaye, S.B.; Poole, C.J.; Dańska-Bidzińska, A.; Gianni, L.; Del Conte, G.; Gorbunova, V.; Novikova, E.; Strauss, A.; Moczko, M.; McNally, V.A.; Ross, G.; Vergote, I. A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. Ann. Oncol., 2013, 24(1), 145-152.
[http://dx.doi.org/10.1093/annonc/mds282] [PMID: 23002282]
[41]
Liu, J.F.; Ray-Coquard, I.; Selle, F.; Poveda, A.M.; Cibula, D.; Hirte, H.; Hilpert, F.; Raspagliesi, F.; Gladieff, L.; Harter, P.; Siena, S.; Del Campo, J.M.; Tabah-Fisch, I.; Pearlberg, J.; Moyo, V.; Riahi, K.; Nering, R.; Kubasek, W.; Adiwijaya, B.; Czibere, A.; Naumann, R.W.; Coleman, R.L.; Vergote, I.; MacBeath, G.; Pujade-Lauraine, E. Randomized phase II trial of seribantumab in combination with paclitaxel in patients with advanced platinum-resistant or -refractory ovarian cancer. J. Clin. Oncol., 2016, 34(36), 4345-4353.
[http://dx.doi.org/10.1200/JCO.2016.67.1891] [PMID: 27998236]
[42]
du Bois, A.; Floquet, A.; Kim, J.W.; Rau, J.; del Campo, J.M.; Friedlander, M.; Pignata, S.; Fujiwara, K.; Vergote, I.; Colombo, N.; Mirza, M.R.; Monk, B.J.; Kimmig, R.; Ray-Coquard, I.; Zang, R.; Diaz-Padilla, I.; Baumann, K.H.; Mouret-Reynier, M.A.; Kim, J.H.; Kurzeder, C.; Lesoin, A.; Vasey, P.; Marth, C.; Canzler, U.; Scambia, G.; Shimada, M.; Calvert, P.; Pujade-Lauraine, E.; Kim, B.G.; Herzog, T.J.; Mitrica, I.; Schade-Brittinger, C.; Wang, Q.; Crescenzo, R.; Harter, P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J. Clin. Oncol., 2014, 32(30), 3374-3382.
[http://dx.doi.org/10.1200/JCO.2014.55.7348] [PMID: 25225436]
[43]
Richardson, D.L.; Sill, M.W.; Coleman, R.L.; Sood, A.K.; Pearl, M.L.; Kehoe, S.M.; Carney, M.E.; Hanjani, P.; Van Le, L.; Zhou, X.C.; Alvarez Secord, A.; Gray, H.J.; Landrum, L.M.; Lankes, H.A.; Hu, W.; Aghajanian, C. 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]
[44]
Sheppard, K.E.; Cullinane, C.; Hannan, K.M.; Wall, M.; Chan, J.; Barber, F.; Foo, J.; Cameron, D.; Neilsen, A.; Ng, P.; Ellul, J.; Kleinschmidt, M.; Kinross, K.M.; Bowtell, D.D.; Christensen, J.G.; Hicks, R.J.; Johnstone, R.W.; McArthur, G.A.; Hannan, R.D.; Phillips, W.A.; Pearson, R.B. Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors. Eur. J. Cancer, 2013, 49(18), 3936-3944.
[http://dx.doi.org/10.1016/j.ejca.2013.08.007] [PMID: 24011934]
[45]
Bardia, A.; Gounder, M.; Rodon, J.; Janku, F.; Lolkema, M.P.; Stephenson, J.J. Phase Ib study of combination therapy with MEK inhibitor binimetinib and phosphatidylinositol 3-kinase inhibitor buparlisib in patients with advanced solid tumors with RAS/RAF alterations. Oncologist, 2019, 24, 1-10.
[PMID: 31395751]
[46]
Bedard, P.L.; Tabernero, J.; Janku, F.; Wainberg, Z.A.; Paz-Ares, L.; Vansteenkiste, J.; Van Cutsem, E.; Pérez-García, J.; Stathis, A.; Britten, C.D.; Le, N.; Carter, K.; Demanse, D.; Csonka, D.; Peters, M.; Zubel, A.; Nauwelaerts, H.; Sessa, C. 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), 730-738.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1814] [PMID: 25500057]
[47]
Simpkins, F.; Jang, K.; Yoon, H.; Hew, K.E.; Kim, M.; Azzam, D.J.; Sun, J.; Zhao, D.; Ince, T.A.; Liu, W.; Guo, W.; Wei, Z.; Zhang, G.; Mills, G.B.; Slingerland, J.M. Dual Src and MEK inhibition decreases ovarian cancer growth and targets tumor initiating stem-like cells. Clin. Cancer Res., 2018, 24(19), 4874-4886.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3697] [PMID: 29959144]
[48]
Iavarone, C.; Zervantonakis, I.K.; Selfors, L.M.; Palakurthi, S.; Liu, J.F.; Drapkin, R.; Matulonis, U.A.; Hallberg, D.; Velculescu, V.E.; Leverson, J.D.; Sampath, D.; Mills, G.B.; Brugge, J.S. Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness. Mol. Cancer Ther., 2019, 18(3), 642-655.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0413] [PMID: 30679390]
[49]
Li, X.; Mak, V.C.Y.; Zhou, Y.; Wang, C.; Wong, E.S.Y.; Sharma, R.; Lu, Y.; Cheung, A.N.Y.; Mills, G.B.; Cheung, L.W.T. Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer. Nat. Commun., 2019, 10(1), 716.
[http://dx.doi.org/10.1038/s41467-019-08574-7] [PMID: 30755611]
[50]
Wang, D.; Li, C.; Zhang, Y.; Wang, M.; Jiang, N.; Xiang, L.; Li, T.; Roberts, T.M.; Zhao, J.J.; Cheng, H.; Liu, P. Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes. Gynecol. Oncol., 2016, 142(3), 548-556.
[http://dx.doi.org/10.1016/j.ygyno.2016.07.092] [PMID: 27426307]
[51]
Matulonis, U.A.; Wulf, G.M.; Barry, W.T.; Birrer, M.; Westin, S.N.; Farooq, S.; Bell-McGuinn, K.M.; Obermayer, E.; Whalen, C.; Spagnoletti, T.; Luo, W.; Liu, H.; Hok, R.C.; Aghajanian, C.; Solit, D.B.; Mills, G.B.; Taylor, B.S.; Won, H.; Berger, M.F.; Palakurthi, S.; Liu, J.; Cantley, L.C.; Winer, E. 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), 512-518.
[http://dx.doi.org/10.1093/annonc/mdw672] [PMID: 27993796]
[52]
Konstantinopoulos, P.A.; Barry, W.T.; Birrer, M.; Westin, S.N.; Cadoo, K.A.; Shapiro, G.I.; Mayer, E.L.; O’Cearbhaill, R.E.; Coleman, R.L.; Kochupurakkal, B.; Whalen, C.; Curtis, J.; Farooq, S.; Luo, W.; Eismann, J.; Buss, M.K.; Aghajanian, C.; Mills, G.B.; Palakurthi, S.; Kirschmeier, P.; Liu, J.; Cantley, L.C.; Kaufmann, S.H.; Swisher, E.M.; D’Andrea, A.D.; Winer, E.; Wulf, G.M.; Matulonis, U.A. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol., 2019, 20(4), 570-580.
[http://dx.doi.org/10.1016/S1470-2045(18)30905-7] [PMID: 30880072]
[53]
Drake, C.G.; Lipson, E.J.; Brahmer, J.R. Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat. Rev. Clin. Oncol., 2014, 11(1), 24-37.
[http://dx.doi.org/10.1038/nrclinonc.2013.208] [PMID: 24247168]
[54]
Leffers, N.; Gooden, M.J.; de Jong, R.A.; Hoogeboom, B.N.; Hoor, K.A.; Hollema, H.; Boezen, H.M.; van der Zee, A.G.; Daemen, T.; Nijman, H.W. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol. Immunother., 2009, 58(3), 449-459.
[http://dx.doi.org/10.1007/s00262-008-0583-5] [PMID: 18791714]
[55]
Marth, C.; Wieser, V.; Tsibulak, I.; Zeimet, A.G. Immunotherapy in ovarian cancer: fake news or the real deal? Int. J. Gynecol. Cancer, 2019, 29(1), 201-211.
[http://dx.doi.org/10.1136/ijgc-2018-000011] [PMID: 30640705]
[56]
Lawrence, M.S.; Stojanov, P.; Polak, P.; Kryukov, G.V.; Cibulskis, K.; Sivachenko, A.; Carter, S.L.; Stewart, C.; Mermel, C.H.; Roberts, S.A.; Kiezun, A.; Hammerman, P.S.; McKenna, A.; Drier, Y.; Zou, L.; Ramos, A.H.; Pugh, T.J.; Stransky, N.; Helman, E.; Kim, J.; Sougnez, C.; Ambrogio, L.; Nickerson, E.; Shefler, E.; Cortés, M.L.; Auclair, D.; Saksena, G.; Voet, D.; Noble, M.; DiCara, D.; Lin, P.; Lichtenstein, L.; Heiman, D.I.; Fennell, T.; Imielinski, M.; Hernandez, B.; Hodis, E.; Baca, S.; Dulak, A.M.; Lohr, J.; Landau, D.A.; Wu, C.J.; Melendez-Zajgla, J.; Hidalgo-Miranda, A.; Koren, A.; McCarroll, S.A.; Mora, J.; Crompton, B.; Onofrio, R.; Parkin, M.; Winckler, W.; Ardlie, K.; Gabriel, S.B.; Roberts, C.W.M.; Biegel, J.A.; Stegmaier, K.; Bass, A.J.; Garraway, L.A.; Meyerson, M.; Golub, T.R.; Gordenin, D.A.; Sunyaev, S.; Lander, E.S.; Getz, G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature, 2013, 499(7457), 214-218.
[http://dx.doi.org/10.1038/nature12213] [PMID: 23770567]
[57]
Shen, J.; Zhao, W.; Ju, Z.; Wang, L.; Peng, Y.; Labrie, M.; Yap, T.A.; Mills, G.B.; Peng, G. PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness. Cancer Res., 2019, 79(2), 311-319.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-1003] [PMID: 30482774]
[58]
Khan, K.A.; Kerbel, R.S. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat. Rev. Clin. Oncol., 2018, 15(5), 310-324.
[http://dx.doi.org/10.1038/nrclinonc.2018.9] [PMID: 29434333]
[59]
Peng, J.; Hamanishi, J.; Matsumura, N.; Abiko, K.; Murat, K.; Baba, T.; Yamaguchi, K.; Horikawa, N.; Hosoe, Y.; Murphy, S.K.; Konishi, I.; Mandai, M. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res., 2015, 75(23), 5034-5045.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3098] [PMID: 26573793]
[60]
Guo, Z.; Wang, H.; Meng, F.; Li, J.; Zhang, S. Combined trabectedin and anti-PD1 antibody produces a synergistic antitumor effect in a murine model of ovarian cancer. J. Transl. Med., 2015, 13, 247.
[http://dx.doi.org/10.1186/s12967-015-0613-y] [PMID: 26219551]
[61]
Hartl, C.A.; Bertschi, A.; Puerto, R.B.; Andresen, C.; Cheney, E.M.; Mittendorf, E.A.; Guerriero, J.L.; Goldberg, M.S. Combination therapy targeting both innate and adaptive immunity improves survival in a pre-clinical model of ovarian cancer. J. Immunother. Cancer, 2019, 7(1), 199.
[http://dx.doi.org/10.1186/s40425-019-0654-5] [PMID: 31362778]
[62]
Higuchi, T.; Flies, D.B.; Marjon, N.A.; Mantia-Smaldone, G.; Ronner, L.; Gimotty, P.A.; Adams, S.F. CTLA-4 blockade synergizes therapeutically with PARP inhibition in BRCA1-deficient ovarian cancer. Cancer Immunol. Res., 2015, 3(11), 1257-1268.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0044] [PMID: 26138335]
[63]
Adams, S.F.; Rixe, O.; McCance, D.; Lee, J.H.; Eberhardt, S.; Westgate, S. Phase I study combining PARP-inhibition with immune checkpoint blockade in women with BRCA-deficient recurrent ovarian cancer. Gynecol. Oncol., 2017, 145, 99-100.
[http://dx.doi.org/10.1016/j.ygyno.2017.03.234]
[64]
Konstantinopoulos, P.A.; Waggoner, S.; Vidal, G.A.; Mita, M.; Moroney, J.W.; Holloway, R.; Van Le, L.; Sachdev, J.C.; Chapman-Davis, E.; Colon-Otero, G.; Penson, R.T.; Matulonis, U.A.; Kim, Y.B.; Moore, K.N.; Swisher, E.M.; Färkkilä, A.; D’Andrea, A.; Stringer-Reasor, E.; Wang, J.; Buerstatte, N.; Arora, S.; Graham, J.R.; Bobilev, D.; Dezube, B.J.; Munster, P. Single-arm phases 1 and 2 Trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol., 2019, 5, 1141-1149.
[http://dx.doi.org/10.1001/jamaoncol.2019.1048] [PMID: 31194228]
[65]
Lee, J.M.; Cimino-Mathews, A.; Peer, C.J.; Zimmer, A.; Lipkowitz, S.; Annunziata, C.M.; Cao, L.; Harrell, M.I.; Swisher, E.M.; Houston, N.; Botesteanu, D.A.; Taube, J.M.; Thompson, E.; Ogurtsova, A.; Xu, H.; Nguyen, J.; Ho, T.W.; Figg, W.D.; Kohn, E.C. Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-Ribose) polymerase inhibitor olaparib or vascular endothelial growth factor receptor 1-3 inhibitor cediranib in women’s cancers: A dose-escalation, phase I study. J. Clin. Oncol., 2017, 35(19), 2193-2202.
[http://dx.doi.org/10.1200/JCO.2016.72.1340] [PMID: 28471727]
[66]
Liu, J.F.; Herold, C.; Gray, K.P.; Penson, R.T.; Horowitz, N.; Konstantinopoulos, P.A.; Castro, C.M.; Hill, S.J.; Curtis, J.; Luo, W.; Matulonis, U.A.; Cannistra, S.A.; Dizon, D.S. Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: A phase 2 clinical trial. JAMA Oncol., 2019, 5, 1731-1738.
[http://dx.doi.org/10.1001/jamaoncol.2019.3343] [PMID: 31600397]
[67]
Odunsi, K.; Matsuzaki, J.; James, S.R.; Mhawech-Fauceglia, P.; Tsuji, T.; Miller, A.; Zhang, W.; Akers, S.N.; Griffiths, E.A.; Miliotto, A.; Beck, A.; Batt, C.A.; Ritter, G.; Lele, S.; Gnjatic, S.; Karpf, A.R. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol. Res., 2014, 2(1), 37-49.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0126] [PMID: 24535937]
[68]
Khan, A.N.; Kolomeyevskaya, N.; Singel, K.L.; Grimm, M.J.; Moysich, K.B.; Daudi, S.; Grzankowski, K.S.; Lele, S.; Ylagan, L.; Webster, G.A.; Abrams, S.I.; Odunsi, K.; Segal, B.H. Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer. Oncotarget, 2015, 6(13), 11310-11326.
[http://dx.doi.org/10.18632/oncotarget.3597] [PMID: 25888637]
[69]
Vermeij, R.; Leffers, N.; Hoogeboom, B.N.; Hamming, I.L.; Wolf, R.; Reyners, A.K.; Molmans, B.H.; Hollema, H.; Bart, J.; Drijfhout, J.W.; Oostendorp, J.; van der Zee, A.G.; Melief, C.J.; van der Burg, S.H.; Daemen, T.; Nijman, H.W. Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: A single-arm phase II study. Int. J. Cancer, 2012, 131(5), E670-E680.
[http://dx.doi.org/10.1002/ijc.27388] [PMID: 22139992]
[70]
Tanyi, J.L.; Bobisse, S.; Ophir, E.; Tuyaerts, S.; Roberti, A.; Genolet, R.; Baumgartner, P.; Stevenson, B.J.; Iseli, C.; Dangaj, D.; Czerniecki, B.; Semilietof, A.; Racle, J.; Michel, A.; Xenarios, I.; Chiang, C.; Monos, D.S.; Torigian, D.A.; Nisenbaum, H.L.; Michielin, O.; June, C.H.; Levine, B.L.; Powell, D.J., Jr; Gfeller, D.; Mick, R.; Dafni, U.; Zoete, V.; Harari, A.; Coukos, G.; Kandalaft, L.E. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med., 2018, 10(436), eaao5931.
[http://dx.doi.org/10.1126/scitranslmed.aao5931] [PMID: 29643231]
[71]
Liu, Z.; Ravindranathan, R.; Kalinski, P.; Guo, Z.S.; Bartlett, D.L. Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nat. Commun., 2017, 8, 14754.
[http://dx.doi.org/10.1038/ncomms14754] [PMID: 28345650]
[72]
Bolyard, C.; Yoo, J.Y.; Wang, P.Y.; Saini, U.; Rath, K.S.; Cripe, T.P.; Zhang, J.; Selvendiran, K.; Kaur, B. Doxorubicin synergizes with 34.5ENVE to enhance antitumor efficacy against metastatic ovarian cancer. Clin. Cancer Res., 2014, 20(24), 6479-6494.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0463] [PMID: 25294909]
[73]
Komorowski, M.P.; McGray, A.R.; Kolakowska, A.; Eng, K.; Gil, M.; Opyrchal, M.; Litwinska, B.; Nemeth, M.J.; Odunsi, K.O.; Kozbor, D. Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy. Mol. Ther. Oncolytics, 2016, 3, 16034.
[http://dx.doi.org/10.1038/mto.2016.34] [PMID: 28035333]
[74]
Matuszewska, K.; Santry, L.A.; van Vloten, J.P.; AuYeung, A.W.K.; Major, P.P.; Lawler, J.; Wootton, S.K.; Bridle, B.W.; Petrik, J. Combining vascular normalization with an oncolytic virus enhances immunotherapy in a preclinical model of advanced-stage ovarian cancer. Clin. Cancer Res., 2019, 25(5), 1624-1638.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0220] [PMID: 30206160]
[75]
Mittica, G.; Capellero, S.; Genta, S.; Cagnazzo, C.; Aglietta, M.; Sangiolo, D.; Valabrega, G. Adoptive immunotherapy against ovarian cancer. J. Ovarian Res., 2016, 9(1), 30.
[http://dx.doi.org/10.1186/s13048-016-0236-9] [PMID: 27188274]
[76]
Wang, W.; Kryczek, I.; Dostál, L.; Lin, H.; Tan, L.; Zhao, L.; Lu, F.; Wei, S.; Maj, T.; Peng, D.; He, G.; Vatan, L.; Szeliga, W.; Kuick, R.; Kotarski, J.; Tarkowski, R.; Dou, Y.; Rattan, R.; Munkarah, A.; Liu, J.R.; Zou, W. Effector T cells abrogate stroma-mediated chemoresistance in ovarian cancer. Cell, 2016, 165(5), 1092-1105.
[http://dx.doi.org/10.1016/j.cell.2016.04.009] [PMID: 27133165]
[77]
Parente-Pereira, A.C.; Whilding, L.M.; Brewig, N.; van der Stegen, S.J.; Davies, D.M.; Wilkie, S.; van Schalkwyk, M.C.; Ghaem-Maghami, S.; Maher, J. Synergistic chemoimmunotherapy of epithelial ovarian cancer using ErbB-retargeted T cells combined with carboplatin. J. Immunol., 2013, 191(5), 2437-2445.
[http://dx.doi.org/10.4049/jimmunol.1301119] [PMID: 23898037]
[78]
Wing, A.; Fajardo, C.A.; Posey, A.D., Jr; Shaw, C.; Da, T.; Young, R.M.; Alemany, R.; June, C.H.; Guedan, S. Improving CART-cell therapy of solid tumors with oncolytic virus-driven production of a bispecific T-cell engager. Cancer Immunol. Res., 2018, 6(5), 605-616.
[http://dx.doi.org/10.1158/2326-6066.CIR-17-0314] [PMID: 29588319]

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