Repurposing Food and Drug Administration-approved cancer therapies: exploring endocrine and targeted pathways in low-grade serous ovarian cancer treatment.

Abstract

Low-grade serous ovarian cancer is a rare epithelial ovarian cancer with limited responsiveness to conventional chemotherapy, particularly, in advanced or recurrent settings. Low-grade serous ovarian cancer is characterized by an indolent growth pattern and a high prevalence of mitogen-activated protein kinase pathway alterations (KRAS, BRAF, NRAS) and hormone receptor positivity, highlighting the potential for targeted therapies. MEK inhibitors (eg, trametinib, binimetinib) specifically target the mitogen-activated protein kinase pathway, whereas endocrine therapies and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors exploit hormone-driven pathways. This review explores the repurposing of the therapeutic potential of both MEK inhibitors and breast cancer therapies, as endorsed by the National Comprehensive Cancer Network, to improve outcomes in low-grade serous ovarian cancer. This review synthesizes evidence supporting the repurposing of MEK inhibitors and breast cancer therapies (endocrine therapies, CDK4/6 inhibitors, and mammalian target of rapamycin inhibitors) as treatment approaches for low-grade serous ovarian cancer. Trametinib significantly improved progression-free survival in the GOG 281 trial, establishing MEK inhibition as a key therapeutic option. In addition, molecular similarities in estrogen receptor/progesterone receptor, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, and CDK4/6 pathways between low-grade serous ovarian cancer and breast cancer provide a strong rationale for therapeutic crossover. Endocrine therapies demonstrated efficacy in low-grade serous ovarian cancer, particularly when combined with targeted agents to address resistance mechanisms. CDK4/6 inhibitors showed promise by blocking cell cycle progression and enhancing the response to endocrine therapies. In addition, mammalian target of rapamycin inhibitors have yielded clinical benefits in selected patients, emphasizing the importance of biomarker-driven treatment. Repurposing MEK inhibitors and endocrine-based approaches is shaping the treatment landscape for low-grade serous ovarian cancer, particularly in recurrent or advanced cases with limited treatment options. However, the variability in pathway alterations necessitates precise molecular profiling and optimized combination strategies. Future studies leveraging patient-derived models and advanced profiling techniques are critical for refining these approaches. These efforts may help expand National Comprehensive Cancer Network-endorsed options, and provide new hope for patients with hormone-sensitive low-grade serous ovarian cancer.