Current perspectives in the pharmacological combination treatment for low-grade serous ovarian cancer

INTRODUCTION: Low-grade serous ovarian carcinoma (LGSOC) is a rare, frequently relapsing ovarian cancer characterized by relative chemoresistance, hormone-receptor expression, and recurrent activation of the RAS/RAF/MEK/ERK pathway. AREAS COVERED: This narrative review examines the therapeutic vulnerabilities that are reshaping systemic treatment in LGSOC. PubMed/MEDLINE and Embase were searched from database inception through July 2026, supplemented by clinical-trial registries and regulatory sources. Endocrine dependence can be targeted with aromatase inhibitors and, increasingly, through combined estrogen-receptor and CDK4/6 blockade. MAPK signaling represents the principal molecular vulnerability: trametinib provides the strongest randomized evidence in recurrent disease, while avutometinib plus defactinib is approved in the United States for previously treated KRAS-mutated LGSOC. The review also considers the evolving role of chemotherapy, antiangiogenic therapy, and molecular biomarkers in treatment selection. EXPERT OPINION: The therapeutic landscape is moving from empiric chemotherapy toward biologically informed treatment. The main challenge is now to define the optimal sequence of endocrine, MAPK-directed, and cell-cycle-targeted therapies according to disease tempo, molecular profile, required tumor shrinkage, prior exposure, and cumulative toxicity. Emerging strategies include combined pathway inhibition, chemotherapy-sparing endocrine regimens, and antibody-drug conjugates directed against FRα and TROP2. Their future integration will require prospective biomarker validation and direct comparison with established active treatments.