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

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.

Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets

“…Clear cell carcinoma (CCC) accounts for approximately 6–10% of EOC [ 15 , 30 ]. CCC progression is strongly associated with endometriosis and benign tumors known as clear cell adenofibromas [ 1 ].…”

Ovarian Cancer Metastasis to the Central Nervous System: A Literature Review

“…This is beneficial as the majority of patients have this variation of cancer, but simultaneously also means that rarer cancers are still understudied on a genetic level [ 43 ]. Novel biomarker candidates are being discovered for rarer cancer types, such as hepatocyte nuclear factor 1β (HNF1β), which is expressed in nearly all cases of ovarian clear cell carcinomas (OCCC) [ 44 ]. As sequencing costs continue to decrease, whole genome sequencing (WGS) analysis will become further utilized in clinical settings.…”

Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis

“…Clear cell carcinoma is characterized by the young age of cases and platinum resistance. However, advanced clear cell carcinoma also has dismal prognosis and a high frequency of associated deaths, largely due to its resistance to chemotherapeutics (3)(4)(5). At present, there is insufficient evidence to develop accurate prognostics strategies for OCCC and therefore, it is of paramount importance that we explore pathological characteristics and prognostic factors to predict outcomes.…”