Therapeutic advances and molecular insights in low-grade serous ovarian carcinoma

Rayan Kabirian & Manuel Rodrigues et al. · 2025-12-15

Low-grade serous ovarian carcinoma is a rare subtype of epithelial ovarian cancer, accounting for less than 10% of serous malignancies. Compared to high-grade serous ovarian carcinoma, it follows an indolent course, often affects younger women, and demonstrates resistance to conventional cytotoxic chemotherapy. Low-grade serous ovarian is characterized by recurrent MAPK pathway alterations (KRAS, BRAF, NRAS) and frequent expression of functional hormone receptors, supporting the rationale for targeted and endocrine strategies. Optimal management relies on complete surgical cytoreduction. Endocrine therapy has shown promise, particularly in maintenance settings, and is being investigated in frontline strategies. MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.
Authors
Rayan Kabirian, Thomas Gaillard, Diana Bello-Roufai, Caroline Malhaire, Virginie Huchet, Céline Callens, Benjamine Pham, Enrica Bentivegna, Bruno Borghese, Enora Laas, Vincent Cockenpot, Alexandra Leary, Jerome Alexandre, Frederic Selle, Manuel Rodrigues