New Advances in Ovarian Clear Cell Carcinoma: from the Mechanism of Drug Resistance to the Selection of Targeted Drugs

doi:10.12280/gjszjk.20200633

Abstract

Abstract:

Ovarian clear cell carcinoma (OCCC) is a relatively rare histological subtype of epithelial ovarian cancer (EOC) with high level of malignant differentiation, low sensitivity to conventional cytotoxic drugs and platinum chemotherapeutic drugs, and poor prognosis. Therefore, it is an urgent clinical problem to find new therapeutic targets for OCCC therapy. The known new molecular targets for OCCC therapy can be divided into four categories: ①AT-rich interactive domain 1A（ARID1A）-related chromatin remodeling errors; ②downstream pathways of receptor tyrosine kinases; ③antioxidant stress molecule; ④immunomodulatory dysfunction. Several inhibitors have been identified. The in vitro and/or in vivo experiments have showed the inhibitory effects on OCCC cells. However, clinical trials did not show sufficient efficacy at present.

Key words: Ovarian neoplasms, Adenocarcinoma, clear cell, Biomarkers, tumor, Drug resistance, neoplasm, ARID1A

DU Yuan-yuan, WANG An-sheng, YANG Yang. New Advances in Ovarian Clear Cell Carcinoma: from the Mechanism of Drug Resistance to the Selection of Targeted Drugs[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(4): 348-352.

References 34

[1]	Korenaga TR, Ward KK, Saenz C, et al. The elevated risk of ovarian clear cell carcinoma among Asian Pacific Islander women in the United States is not affected by birthplace[J]. Gynecol Oncol, 2020, 157(1):62-66. doi: 10.1016/j.ygyno.2020.01.034. doi: 10.1016/j.ygyno.2020.01.034 URL
[2]	Tan TZ, Ye J, Yee CV, et al. Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes[J]. EBioMedicine, 2019, 50:203-210. doi: 10.1016/j.ebiom.2019.11.017. doi: 10.1016/j.ebiom.2019.11.017 URL
[3]	Fukumoto T, Fatkhutdinov N, Zundell JA, et al. HDAC6 Inhibition Synergizes with Anti-PD-L1 Therapy in ARID1A-Inactivated Ovarian Cancer[J]. Cancer Res, 2019, 79(21):5482-5489. doi: 10.1158/0008-5472.CAN-19-1302. doi: 10.1158/0008-5472.CAN-19-1302 pmid: 31311810
[4]	张凯丽. 靶向EZH2-EED相互作用抑制剂的发现及抗肿瘤机制研究[D]. 上海:中国科学院大学(中国科学院上海药物研究所), 2019.
[5]	Kelso TWR, Porter DK, Amaral ML, et al. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers[J]. Elife, 2017, 6:e30506. doi: 10.7554/eLife.30506. doi: 10.7554/eLife.30506 URL
[6]	Amano T, Chano T, Yoshino F, et al. Current Position of the Molecular Therapeutic Targets for Ovarian Clear Cell Carcinoma: A Literature Review[J]. Healthcare (Basel), 2019, 7(3):94. doi: 10.3390/healthcare7030094. doi: 10.3390/healthcare7030094
[7]	Ogiwara H, Takahashi K, Sasaki M, et al. Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Cancers[J]. Cancer Cell, 2019, 35(2):177-190. e8. doi: 10.1016/j.ccell.2018.12.009. doi: 10.1016/j.ccell.2018.12.009 URL
[8]	Novera W, Lee ZW, Nin DS, et al. Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit[J]. Antioxid Redox Signal, 2020, 33(17):1191-1208. doi: 10.1089/ars.2019.7850. doi: 10.1089/ars.2019.7850 URL
[9]	Oda K, Hamanishi J, Matsuo K, et al. Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management[J]. Gynecol Oncol, 2018, 151(2):381-389. doi: 10.1016/j.ygyno.2018.09.001. doi: 10.1016/j.ygyno.2018.09.001 URL
[10]	Mathur R. ARID1A loss in cancer: Towards a mechanistic understanding[J]. Pharmacol Ther, 2018, 190:15-23. doi: 10.1016/j.pharmthera.2018.05.001. doi: 10.1016/j.pharmthera.2018.05.001 URL
[11]	Kuroda T, Ogiwara H, Sasaki M, et al. Therapeutic preferability of gemcitabine for ARID1A-deficient ovarian clear cell carcinoma[J]. Gynecol Oncol, 2019, 155(3):489-498. doi: 10.1016/j.ygyno.2019. 10.002. doi: 10.1016/j.ygyno.2019. 10.002 URL
[12]	Ke B, Chen Y, Tu W, et al. Inhibition of HDAC6 activity in kidney diseases: a new perspective[J]. Mol Med, 2018, 24(1):33. doi: 10.1186/s10020-018-0027-4. doi: 10.1186/s10020-018-0027-4 URL
[13]	Lee YS, Lim KH, Guo X, et al. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis[J]. Cancer Res, 2008, 68(18):7561-7569. doi: 10.1158/0008-5472.CAN-08-0188. doi: 10.1158/0008-5472.CAN-08-0188 URL
[14]	Fukumoto T, Fatkhutdinov N, Zundell JA, et al. HDAC6 Inhibition Synergizes with Anti-PD-L1 Therapy in ARID1A-Inactivated Ovarian Cancer[J]. Cancer Res, 2019, 79(21):5482-5489. doi: 10.1158/0008-5472.CAN-19-1302. doi: 10.1158/0008-5472.CAN-19-1302 pmid: 31311810
[15]	Kadoch C, Williams RT, Calarco JP, et al. Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states[J]. Nat Genet, 2017, 49(2):213-222. doi: 10.1038/ng.3734. doi: 10.1038/ng.3734 URL
[16]	Bitler BG, Aird KM, Garipov A, et al. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers[J]. Nat Med, 2015, 21(3):231-238. doi: 10.1038/nm.3799. doi: 10.1038/nm.3799
[17]	Bitler BG, Fatkhutdinov N, Zhang R. Potential therapeutic targets in ARID1A-mutated cancers[J]. Expert Opin Ther Targets, 2015, 19(11):1419-1422. doi: 10.1517/14728222.2015.1062879. doi: 10.1517/14728222.2015.1062879 URL
[18]	武博荣, 金萌, 王卫真, 等. PI3K/AKT信号通路在肿瘤调控中的免疫作用及分子机制[J]. 临床合理用药杂志, 2013, 6(6A):135-137. doi: 10.3969/j.issn.1674-3296.2013.16.112. doi: 10.3969/j.issn.1674-3296.2013.16.112
[19]	Arechavaleta-Velasco F, Perez-Juarez CE, Gerton GL, et al. Progranulin and its biological effects in cancer[J]. Med Oncol, 2017, 34(12):194. doi: 10.1007/s12032-017-1054-7. doi: 10.1007/s12032-017-1054-7 pmid: 29116422
[20]	Perez-Juarez CE, Arechavaleta-Velasco F, Zeferino-Toquero M, et al. Inhibition of PI3K/AKT/mTOR and MAPK signaling pathways decreases progranulin expression in ovarian clear cell carcinoma (OCCC) cell line: a potential biomarker for therapy response to signaling pathway inhibitors[J]. Med Oncol, 2019, 37(1):4. doi: 10.1007/s12032-019-1326-5. doi: 10.1007/s12032-019-1326-5 pmid: 31713081
[21]	Wakinoue S, Chano T, Amano T, et al. ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers[J]. Cancer Biomark, 2019, 24(2):223-229. doi: 10.3233/CBM-181836. doi: 10.3233/CBM-181836 pmid: 30594917
[22]	Matsumoto S, Fujii S, Sato A, et al. A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures[J]. EMBO J, 2014, 33(7):702-718. doi: 10.1002/embj.201386942. doi: 10.1002/embj.201386942 URL
[23]	Fujii S, Matsumoto S, Nojima S, et al. Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target[J]. Oncogene, 2015, 34(37):4834-4844. doi: 10.1038/onc.2014.402. doi: 10.1038/onc.2014.402 pmid: 25486429
[24]	Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?[J]. Nat Rev Drug Discov, 2009, 8(7):579-591. doi: 10.1038/nrd2803. doi: 10.1038/nrd2803 pmid: 19478820
[25]	Yamaguchi K, Mandai M, Oura T, et al. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes[J]. Oncogene, 2010, 29(12):1741-1752. doi: 10.1038/onc.2009.470. doi: 10.1038/onc.2009.470 pmid: 20062075
[26]	Koppula P, Zhang Y, Shi J, et al. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate[J]. J Biol Chem, 2017, 292(34):14240-14249. doi: 10.1074/jbc.M117.798405. doi: 10.1074/jbc.M117.798405 URL
[27]	Sasaki M, Chiwaki F, Kuroda T, et al. Efficacy of glutathione inhibitors for the treatment of ARID1A-deficient diffuse-type gastric cancers[J]. Biochem Biophys Res Commun, 2020, 522(2):342-347. doi: 10.1016/j.bbrc.2019.11.078. doi: 10.1016/j.bbrc.2019.11.078 URL
[28]	Bykov VJ, Zhang Q, Zhang M, et al. Targeting of Mutant p53 and the Cellular Redox Balance by APR-246 as a Strategy for Efficient Cancer Therapy[J]. Front Oncol, 2016, 6:21. doi: 10.3389/fonc.2016.00021. doi: 10.3389/fonc.2016.00021
[29]	李宽钰. 线粒体铁代谢与人类疾病的基础研究[J]. 医学研究生学报, 2016, 29(1):24-28. doi: 10.16571/j.cnki.1008-8199.2016. 01.006. doi: 10.16571/j.cnki.1008-8199.2016. 01.006
[30]	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5):1060-1072. doi: 10.1016/j.cell.2012.03.042. doi: 10.1016/j.cell.2012.03.042 URL
[31]	Parazzini F, Esposito G, Tozzi L, et al. Epidemiology of endometriosis and its comorbidities[J]. Eur J Obstet Gynecol Reprod Biol, 2017, 209:3-7. doi: 10.1016/j.ejogrb.2016.04.021. doi: 10.1016/j.ejogrb.2016.04.021 URL
[32]	Oda K, Hamanishi J, Matsuo K, et al. Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management[J]. Gynecol Oncol, 2018, 151(2):381-389. doi: 10.1016/j.ygyno.2018.09.001. doi: 10.1016/j.ygyno.2018.09.001 URL
[33]	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[J]. Ann Oncol, 2019, 30(7):1080-1087. doi: 10.1093/annonc/mdz135. doi: S0923-7534(19)31241-4 pmid: 31987374
[34]	Hamanishi J, Mandai M, Ikeda T, et al. Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer[J]. J Clin Oncol, 2015, 33(34):4015-4022. doi: 10.1200/JCO.2015.62.3397. doi: 10.1200/JCO.2015.62.3397 pmid: 26351349