This review aims to consolidate the current understanding of Clear Cell Ovarian Carcinoma (CCOC), a rare yet distinct subtype of epithelial ovarian cancer. CCOC exhibits unique epidemiological, clinical and molecular features, being one of the most frequent subtypes in East Asia, often diagnosed at an early stage and frequently affecting younger women. Its hallmark characteristics include high resistance to conventional chemotherapy, poor prognosis in advanced stage and a molecular profile distinct from high-grade serous histotype. Specifically, CCOC is characterized by a low prevalence of TP53 mutations, BRCA1/2 mutations and homologous-recombination deficiency, but a high frequency of ARID1A, along with other SWI/SNF alterations, and PIK3CA mutations, both of which represent promising therapeutic targets. Despite the absence of validated therapies for CCOC so far, significant advancements in preclinical research and emerging clinical strategies including immunotherapy combinations offer hope for improved outcomes. Given the rarity of this cancer type, collaborative research and global partnerships have enabled robust studies and the implementation of trials with innovative personalized therapeutic approaches. The objective of this report is to explore the epidemiology, clinical and molecular characteristics, current standard of care and evolving therapeutic strategies for CCOC patients. It will not only highlight the progress made so far, but most importantly identifies critical research priorities to optimizing patient outcomes.
Keywords: Clear cell carcinoma; Immunotherapy; Molecular pathology; Ovarian Cancer; Personalized medicine.
Copyright © 2025. Published by Elsevier Ltd.
