Molecular profile and targeted therapies for ovarian clear cell ovarian cancer

Ovarian clear cell carcinoma (OCCC) is a distinct epithelial ovarian cancer subtype with unique molecular features, and a notable resistance to conventional platinum-based chemotherapy in advanced disease. Key molecular hallmarks include frequent ARID1A loss and PIK3CA activation, which often co-occur and contribute to early tumorigenesis. Emerging targeted therapies—including anti-angiogenic agents, immune checkpoint inhibitors, ATR and PI3K pathway inhibitors, and antibody-drug conjugates—demonstrate promising activity, particularly in molecularly defined subgroups, though most evidence to date remains largely limited to early-phase trials. Given its rarity, chemoresistance, and underrepresentation in large trials, OCCC requires histology-specific therapeutic strategies informed by molecular profiling. Ongoing research into biomarker-driven therapies and combination regimens holds the potential to transform outcomes for this challenging ovarian cancer subtype.