Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

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

Review Article

揭示三阴性乳腺癌的新型治疗药物靶点和预后标志物

卷 21, 期 11, 2021

发表于: 26 November, 2021

页: [907 - 918] 页: 12

弟呕挨: 10.2174/1568009621666210908113010

价格: $65

摘要

三阴性乳腺癌代表多种基因组和转录组异质性。 TNBC 中出现的遗传和表观遗传变化有助于它获得对免疫反应的抵抗力。远处转移、缺乏临床靶向治疗和预后标志物使其成为最具侵袭性的乳腺癌形式。在这篇综述中,我们发现靶向基因 AR、ERR、TIL、TAM、miRNA、mTOR 和免疫抑制细胞因子的驱动改变主要通过诱导细胞增殖、侵袭和转移以及抑制细胞凋亡参与了 TNBC 的并发症。还研究了淋巴结状态、组织蛋白酶-D、Ki-67 指数、CD3+TIL、BRCA1 启动子甲基化值和 p53 作为有效预后因素的作用,以预测 TNBC 患者的无病生存率和总生存率。本综述文章试图以新的视角了解 TNBC 的病因、治疗策略和预后标志物,以确定标准治疗的结果,并重新设计未来的治疗策略,为患者提供最大的益处。

关键词: AR、microRNAs、TAM、TNBC、TILs、治疗、预后。

图形摘要

[1]
Arnedos, M.; Bihan, C.; Delaloge, S.; Andre, F. Triple-negative breast cancer: are we making headway at least? Ther. Adv. Med. Oncol., 2012, 4(4), 195-210.
[http://dx.doi.org/10.1177/1758834012444711] [PMID: 22754593]
[2]
Schmadeka, R.; Harmon, B.E.; Singh, M. Triple-negative breast carcinoma: current and emerging concepts. Amer. Clin. Path., 2014, 141(4), 462-477.
[http://dx.doi.org/10.1309/AJCPQN8GZ8SILKGN] [PMID: 24619745]
[3]
Lehmann, B.D.; Bauer, J.A.; Chen, X.; Sanders, M.E.; Chakravarthy, A.B.; Shyr, Y.; Pietenpol, J.A. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest., 2011, 121(7), 2750-2767.
[http://dx.doi.org/10.1172/JCI45014] [PMID: 21633166]
[4]
Barton, V.N.; D’Amato, N.C.; Gordon, M.A.; Lind, H.T.; Spoelstra, N.S.; Babbs, B.L.; Heinz, R.E.; Elias, A.; Jedlicka, P.; Jacobsen, B.M.; Richer, J.K. Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo. Mol. Cancer Ther., 2015, 14(3), 769-778.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0926] [PMID: 25713333]
[5]
Stagg, J.; Allard, B. Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects. Ther. Adv. Med. Oncol., 2013, 5(3), 169-181.
[http://dx.doi.org/10.1177/1758834012475152] [PMID: 23634195]
[6]
Balkrishna, A.; Mittal, R.; Arya, V. Unveiling role of MicroRNAs as treatment strategy and prognostic markers in triple negative breast cancer. Curr. Pharm. Biotechnol., 2020, 21(15), 1569-1575.
[http://dx.doi.org/10.2174/1389201021666200627201535] [PMID: 32593278]
[7]
Treeck, O.; Schüler-Toprak, S.; Ortmann, O. Estrogen actions in triple-negative breast cancer. Cells, 2020, 9(11), 2358.
[http://dx.doi.org/10.3390/cells9112358] [PMID: 33114740]
[8]
Maniscalco, L.; Millán, Y.; Iussich, S.; Denina, M.; Sánchez-Céspedes, R.; Gattino, F.; Biolatti, B.; Sasaki, N.; Nakagawa, T.; Di Renzo, M.F.; de Las Mulas, J.M.; De Maria, R. Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas. BMC Vet. Res., 2013, 9(1), 80.
[http://dx.doi.org/10.1186/1746-6148-9-80] [PMID: 23587222]
[9]
Kim, J.Y.; Jung, H.H.; Ahn, S.; Bae, S.; Lee, S.K.; Kim, S.W.; Lee, J.E.; Nam, S.J.; Ahn, J.S.; Im, Y.H.; Park, Y.H. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment. Sci. Rep., 2016.
[http://dx.doi.org/10.1038/srep31804]
[10]
Kwon, J.; Eom, K.Y.; Koo, T.R.; Kim, B.H.; Kang, E.; Kim, S.W.; Kim, Y.J.; Park, S.Y.; Kim, I.A. A prognostic model for patients with triple-negative breast cancer: importance of the modified nottingham prognostic index and age. J. Breast Cancer, 2017, 20(1), 65-73.
[http://dx.doi.org/10.4048/jbc.2017.20.1.65] [PMID: 28382096]
[11]
Yao, L.; Liu, Y.; Cao, Z.; Li, J.; Huang, Y.; Hu, X.; Shao, Z. MicroRNA-493 is a prognostic factor in triple-negative breast cancer. Cancer Sci., 2018, 109(7), 2294-2301.
[http://dx.doi.org/10.1111/cas.13644] [PMID: 29777630]
[12]
Chen, X.; Li, J.; Gray, W.H.; Lehmann, B.D.; Bauer, J.A.; Shyr, Y.; Pietenpol, J.A. TNBC type: a subtyping tool for triple-negative breast cancer. Cancer Inform., 2012, 11, 147-156.
[http://dx.doi.org/10.4137/CIN.S9983] [PMID: 22872785]
[13]
Bauer, J.A.; Chakravarthy, A.B.; Rosenbluth, J.M.; Mi, D.; Seeley, E.H.; De Matos Granja-Ingram, N.; Olivares, M.G.; Kelley, M.C.; Mayer, I.A.; Meszoely, I.M.; Means-Powell, J.A.; Johnson, K.N.; Tsai, C.J.; Ayers, G.D.; Sanders, M.E.; Schneider, R.J.; Formenti, S.C.; Caprioli, R.M.; Pietenpol, J.A. Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin. Cancer Res., 2010, 16(2), 681-690.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1091] [PMID: 20068102]
[14]
Juul, N.; Szallasi, Z.; Eklund, A.C.; Li, Q.; Burrell, R.A.; Gerlinger, M.; Valero, V.; Andreopoulou, E.; Esteva, F.J.; Symmans, W.F.; Desmedt, C.; Haibe-Kains, B.; Sotiriou, C.; Pusztai, L.; Swanton, C. Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials. Lancet Oncol., 2010, 11(4), 358-365.
[http://dx.doi.org/10.1016/S1470-2045(10)70018-8] [PMID: 20189874]
[15]
Mayer, I.A. A phase II newoadjuvant negative (TN) locally advanced breast cancer (BC). J. Clin. Oncol., 2010, 28(1), 15.
[PMID: 19933920]
[16]
Bertucci, F.; Finetti, P.; Cervera, N.; Charafe-Jauffret, E.; Mamessier, E.; Adélaïde, J.; Debono, S.; Houvenaeghel, G.; Maraninchi, D.; Viens, P.; Charpin, C.; Jacquemier, J.; Birnbaum, D. Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res., 2006, 66(9), 4636-4644.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0031] [PMID: 16651414]
[17]
Gibson, G.R.; Qian, D.; Ku, J.K.; Lai, L.L. Metaplastic breast cancer: clinical features and outcomes. Am. Surg., 2005, 71(9), 725-730.
[http://dx.doi.org/10.1177/000313480507100906] [PMID: 16468506]
[18]
Prat, A.; Parker, J.S.; Karginova, O.; Fan, C.; Livasy, C.; Herschkowitz, J.I.; He, X.; Perou, C.M. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res., 2010, 12(5), R68.
[http://dx.doi.org/10.1186/bcr2635] [PMID: 20813035]
[19]
Hayes, M.J.; Thomas, D.; Emmons, A.; Giordano, T.J.; Kleer, C.G. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin. Cancer Res., 2008, 14(13), 4038-4044.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-4379] [PMID: 18593979]
[20]
Chen, C.D.; Welsbie, D.S.; Tran, C.; Baek, S.H.; Chen, R.; Vessella, R.; Rosenfeld, M.G.; Sawyers, C.L. Molecular determinants of resistance to antiandrogen therapy. Nat. Med., 2004, 10(1), 33-39.
[http://dx.doi.org/10.1038/nm972] [PMID: 14702632]
[21]
Farmer, P.; Bonnefoi, H.; Becette, V.; Tubiana-Hulin, M.; Fumoleau, P.; Larsimont, D.; Macgrogan, G.; Bergh, J.; Cameron, D.; Goldstein, D.; Duss, S.; Nicoulaz, A.L.; Brisken, C.; Fiche, M.; Delorenzi, M.; Iggo, R. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene, 2005, 24(29), 4660-4671.
[http://dx.doi.org/10.1038/sj.onc.1208561] [PMID: 15897907]
[22]
Ring, BZ.; Hout, DR.; Morris, SW.; Lawrence, K.; Schweitzer, BL.; Bailey, DB.; Lehmann, BD.; Pietenpol, JA.; Seitz, RS. Generation of an algorithm based on minimal gene sets to clinically subtype triple negative breast cancer patients. BMC Cancer, 2016, 16(1), 143.
[23]
Rampurwala, M.; Wisinski, K.B.; O’Regan, R. Role of the androgen receptor in triple-negative breast cancer. Clin. Adv. Hematol. Oncol., 2016, 14(3), 186-193.
[PMID: 27058032]
[24]
Bonnefoi, H.; Grellety, T.; Tredan, O.; Saghatchian, M.; Dalenc, F.; Mailliez, A.; L’Haridon, T.; Cottu, P.; Abadie-Lacourtoisie, S.; You, B.; Mousseau, M.; Dauba, J.; Del Piano, F.; Desmoulins, I.; Coussy, F.; Madranges, N.; Grenier, J.; Bidard, F.C.; Proudhon, C.; MacGrogan, G.; Orsini, C.; Pulido, M.; Gonçalves, A. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann. Oncol., 2016, 27(5), 812-818.
[http://dx.doi.org/10.1093/annonc/mdw067] [PMID: 27052658]
[25]
Zhu, A.; Li, Y.; Song, W.; Xu, Y.; Yang, F.; Zhang, W.; Yin, Y.; Guan, X. Antiproliferative effect of androgen receptor inhibition in mesenchymal stem-like triple-negative breast cancer. Cell. Physiol. Biochem., 2016, 38(3), 1003-1014.
[http://dx.doi.org/10.1159/000443052] [PMID: 26938985]
[26]
Caiazza, F.; Murray, A.; Madden, S.F.; Synnott, N.C.; Ryan, E.J.; O’Donovan, N.; Crown, J.; Duffy, M.J. Preclinical evaluation of the AR inhibitor enzalutamide in triple-negative breast cancer cells. End. Rel. Cancer, 2016, 23(4), 323-334.
[http://dx.doi.org/10.1530/ERC-16-0068] [PMID: 26932782]
[27]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[28]
Qiao, Y.; He, H.; Jonsson, P.; Sinha, I.; Zhao, C.; Dahlman-Wright, K. AP-1 is a key regulator of proinflammatory cytokine TNFα-mediated triple-negative breast cancer progression. J. Biol. Chem., 2016, 291(10), 5068-5079.
[http://dx.doi.org/10.1074/jbc.M115.702571] [PMID: 26792858]
[29]
Wang, J.; Chen, H.; Chen, X.; Lin, H. Expression of Tumor-Related Macrophages and Cytokines After Surgery of Triple-Negative Breast Cancer Patients and its Implications. Med. Sci. Monit., 2016, 22, 115-120.
[http://dx.doi.org/10.12659/MSM.895386] [PMID: 26752006]
[30]
García-Teijido, P.; Cabal, M.L.; Fernández, I.P.; Pérez, Y.F. Tumor-infiltrating lymphocytes in triple negative breast cancer: The future of immune targeting. Clin. Med. Ins. Oncol, 2016.
[31]
Browne, G.; Dragon, J.A.; Hong, D.; Messier, T.L.; Gordon, J.A.; Farina, N.H.; Boyd, J.R.; VanOudenhove, J.J.; Perez, A.W.; Zaidi, S.K.; Stein, J.L.; Stein, G.S.; Lian, J.B. MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells. Tumour Biol., 2016, 37(7), 8825-8839.
[http://dx.doi.org/10.1007/s13277-015-4710-6] [PMID: 26749280]
[32]
Adams, B.D.; Wali, V.B.; Cheng, C.J.; Inukai, S.; Booth, C.J.; Agarwal, S.; Rimm, D.L.; Győrffy, B.; Santarpia, L.; Pusztai, L.; Saltzman, W.M.; Slack, F.J. MiR-34a silences c-SRC to attenuate tumor growth in triple-negative breast cancer. Cancer Res., 2016, 76(4), 927-939.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2321] [PMID: 26676753]
[33]
Phan, B.; Majid, S.; Ursu, S.; de Semir, D.; Nosrati, M.; Bezrookove, V.; Kashani-Sabet, M.; Dar, A.A. Tumor suppressor role of microRNA-1296 in triple-negative breast cancer. Oncotarget, 2016, 7(15), 19519-19530.
[http://dx.doi.org/10.18632/oncotarget.6961] [PMID: 26799586]
[34]
Yan, M.; Li, X.; Tong, D.; Han, C.; Zhao, R.; He, Y.; Jin, X. miR-136 suppresses tumor invasion and metastasis by targeting RASAL2 in triple-negative breast cancer. Oncol. Rep., 2016, 36(1), 65-71.
[http://dx.doi.org/10.3892/or.2016.4767] [PMID: 27108696]
[35]
Wu, Y.M.; Chen, Z.J.; Jiang, G.M.; Zhang, K.S.; Liu, Q.; Liang, S.W.; Zhou, Y.; Huang, H.B.; Du, J.; Wang, H.S. Inverse agonist of estrogen-related receptor α suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways. Oncotarget, 2016, 7(11), 12568-12581.
[http://dx.doi.org/10.18632/oncotarget.7276] [PMID: 26871469]
[36]
Pikarsky, E.; Porat, R.M.; Stein, I.; Abramovitch, R.; Amit, S.; Kasem, S.; Gutkovich-Pyest, E.; Urieli-Shoval, S.; Galun, E.; Ben-Neriah, Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature, 2004, 431(7007), 461-466.
[http://dx.doi.org/10.1038/nature02924] [PMID: 15329734]
[37]
Wang, C.Y.; Mayo, M.W.; Baldwin, A.S., Jr TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kB. Science, 1996.
[http://dx.doi.org/10.1126/science.274.5288.784]
[38]
Chen, YJ.; Yeh, MH.; Yu, MC.; Wei, YL.; Chen, WS.; Chen, JY.; Shih, CY.; Tu, CY.; Chen, CH.; Hsia, TC.; Chien, PH. Lapatinib–induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. Breast Cancer Res., 2013, 15(6), 1.
[http://dx.doi.org/10.1186/bcr3575]
[39]
Manning, BD.; Cantley, LC. AKT/PKB signaling: navigating downstream. Cell, 2007, 129(7), 1261-1274.
[40]
Rubio-Viqueira, B.; Hidalgo, M. Targeting mTOR for cancer treatment. In: New trends in cancer for the 21st century; Springer: Netherlands, 2006; pp. 309-327.
[http://dx.doi.org/10.1007/978-1-4020-5133-3_24]
[41]
Zhang, H.; Cohen, AL.; Krishnakumar, S.; Wapnir, IL.; Veeriah, S.; Deng, G.; Coram, MA.; Piskun, CM.; Longacre, TA.; Herrler, M.; Frimannsson, DO. Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition. Breast Cancer Res., 2014, 16(2), R36.
[http://dx.doi.org/10.1186/bcr3640]
[42]
Singh, J.; Novik, Y.; Stein, S.; Volm, M.; Meyers, M.; Smith, J.; Omene, C.; Speyer, J.; Schneider, R.; Jhaveri, K.; Formenti, S.; Kyriakou, V.; Joseph, B.; Goldberg, J.D.; Li, X.; Adams, S.; Tiersten, A. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer. Breast Cancer Res., 2014, 16(2), R32.
[http://dx.doi.org/10.1186/bcr3634] [PMID: 24684785]
[43]
Moestue, S.A.; Dam, C.G.; Gorad, S.S.; Kristian, A.; Bofin, A.; Mælandsmo, G.M.; Engebråten, O.; Gribbestad, I.S.; Bjørkøy, G. Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer. Breast Cancer Res., 2013, 15(1), R16.
[http://dx.doi.org/10.1186/bcr3391] [PMID: 23448424]
[44]
Ellard, S.L.; Clemons, M.; Gelmon, K.A.; Norris, B.; Kennecke, H.; Chia, S.; Pritchard, K.; Eisen, A.; Vandenberg, T.; Taylor, M.; Sauerbrei, E.; Mishaeli, M.; Huntsman, D.; Walsh, W.; Olivo, M.; McIntosh, L.; Seymour, L. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J. Clin. Oncol., 2009, 27(27), 4536-4541.
[http://dx.doi.org/10.1200/JCO.2008.21.3033] [PMID: 19687332]
[45]
Hart, S.; Novotny-Diermayr, V.; Goh, K.C.; Williams, M.; Tan, Y.C.; Ong, L.C.; Cheong, A.; Ng, B.K.; Amalini, C.; Madan, B.; Nagaraj, H.; Jayaraman, R.; Pasha, K.M.; Ethirajulu, K.; Chng, W.J.; Mustafa, N.; Goh, B.C.; Benes, C.; McDermott, U.; Garnett, M.; Dymock, B.; Wood, J.M. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol. Cancer Ther., 2013, 12(2), 151-161.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0466] [PMID: 23270925]
[46]
Liang, D.H.; Choi, D.S.; Ensor, J.E.; Kaipparettu, B.A.; Bass, B.L.; Chang, J.C. The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair. Cancer Lett., 2016, 376(2), 249-258.
[http://dx.doi.org/10.1016/j.canlet.2016.04.002] [PMID: 27060208]
[47]
Zhou, X.; Jiao, D.; Dou, M.; Zhang, W.; Lv, L.; Chen, J.; Li, L.; Wang, L.; Han, X. Curcumin inhibits the growth of triple-negative breast cancer cells by silencing EZH2 and restoring DLC1 expression. J. Cell. Mol. Med., 2020, 24(18), 10648-10662.
[http://dx.doi.org/10.1111/jcmm.15683] [PMID: 32725802]
[48]
Huang, L.; Liu, Z.; Chen, S.; Liu, Y.; Shao, Z. A prognostic model for triple-negative breast cancer patients based on node status, cathepsin-D and Ki-67 index. PLoS One, 2013, 8(12), e83081.
[http://dx.doi.org/10.1371/journal.pone.0083081] [PMID: 24340082]
[49]
Rathore, A.S.; Goel, M.M.; Makker, A.; Kumar, S.; Srivastava, V. Prognostic impact of CD3 tumor infiltrating lymphocytes in triple-negative breast cancer. Oncology, 2013, CD3.
[50]
Fulford, L.G.; Reis-Filho, J.S.; Ryder, K.; Jones, C.; Gillett, C.E.; Hanby, A.; Easton, D.; Lakhani, S.R. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res., 2007, 9(1), R4.
[http://dx.doi.org/10.1186/bcr1636] [PMID: 17217540]
[51]
Rodríguez-Pinilla, S.M.; Sarrió, D.; Honrado, E.; Hardisson, D.; Calero, F.; Benitez, J.; Palacios, J. Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clin. Cancer Res., 2006, 12(5), 1533-1539.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2281] [PMID: 16533778]
[52]
Guo, X.; Fan, Y.; Lang, R.; Gu, F.; Chen, L.; Cui, L.; Pringle, G.A.; Zhang, X.; Fu, L. Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast. Mod. Pathol., 2008, 21(9), 1101-1107.
[http://dx.doi.org/10.1038/modpathol.2008.72] [PMID: 18469794]
[53]
Rabinowich, H.; Cohen, R.; Bruderman, I.; Steiner, Z.; Klajman, A. Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res., 1987, 47(1), 173-177.
[PMID: 3491673]
[54]
Topalian, S.L.; Solomon, D.; Rosenberg, S.A. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J. Immunol., 1989, 142(10), 3714-3725.
[PMID: 2785562]
[55]
Sharma, P.; Stecklein, S.R.; Kimler, B.F.; Sethi, G.; Petroff, B.K.; Phillips, T.A.; Tawfik, O.W.; Godwin, A.K.; Jensen, R.A. The prognostic value of BRCA1 promoter methylation in early stage triple negative breast cancer. J. Cancer Ther. Res., 2014, 3(2), 1-11.
[http://dx.doi.org/10.7243/2049-7962-3-2] [PMID: 25177489]
[56]
Chae, B.J.; Bae, J.S.; Lee, A.; Park, W.C.; Seo, Y.J.; Song, B.J.; Kim, J.S.; Jung, S.S. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn. J. Clin. Oncol., 2009, 39(4), 217-224.
[http://dx.doi.org/10.1093/jjco/hyp007] [PMID: 19304743]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy