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J Cancer 2021; 12(8):2295-2316. doi:10.7150/jca.53395 This issue Cite

Review

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

Chenchen Zhu^1#, Zhihao Xu^2#, Tianjiao Zhang^2#, Lili Qian², Weihua Xiao^3,4, Haiming Wei^3,4, Tengchuan Jin^2✉, Ying Zhou^1,2✉

1. Department of Obstetrics and Gynecology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
3. Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China.
4. Institute of Immunology, University of Science and Technology of China, Hefei, China.
#Co-first authors.

✉ Corresponding authors: Tengchuan Jin, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China. E-mail: jintedu.cn; Telephone number: +86-0551-63600720; Ying Zhou, Department of Obstetrics and Gynecology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, 230001, China. E-mail: caddiezyedu.cn; Telephone number: +86-0551-62283954. More

Abstract

Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC) and has a high prevalence in Asia without specific molecular subtype classification. Endometriosis is a recognized precancerous lesion that carries 3-fold increased risk of OCCC. Ovarian endometrioid carcinoma, which also originates from endometriosis, shares several features with OCCC, including platinum resistance and younger age at diagnosis. Patients with OCCC have about a 2.5 to 4 times greater risk of having a venous thromboembolism (VTE) compared with other EOC, and OCCC tends to metastasize through lymphatic vesicular and peritoneal spread as opposed to hematogenous metastasis. There is only mild elevation of the conventional biomarker CA125. Staging surgery or optimal cytoreduction combined with chemotherapy is a common therapeutic strategy for OCCC. However, platinum resistance commonly portends a poor prognosis, so novel treatments are urgently needed. Targeted therapy and immunotherapy are currently being studied, including PARP, EZH2, and ATR inhibitors combined with the synthetic lethality of ARID1A-dificiency, and MAPK/PI3K/HER2, VEGF/bFGF/PDGF, HNF1β, and PD-1/PD-L1 inhibitors. Advanced stage, suboptimal cytoreduction, platinum resistance, lymph node metastasis, and VTE are major prognostic predictors for OCCC. We focus on update pathogenesis, diagnostic methods and therapeutic approaches to provide future directions for clinical diagnosis and treatment of OCCC.

Keywords: Ovarian clear cell carcinoma, epithelial ovarian carcinoma, endometriosis, targeted treatment

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