Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Although initial response rates to standard platinum-based treatment are at 70-80%, long-term response in advanced EOC disease is rarely achieved with the development of chemoresistance and recurrence, contributing to overall survival rates below 45%. Additional challenges stem from EOC heterogeneity, reflecting at least five histological subtypes, each with different underlying molecular characteristics and clinicopathology that have significant implications in treatment effectiveness and management. Since the last decade, technologies in genomics, proteomics and pathology have been deployed to find reliable clinical markers that can identify patients sensitive to standard chemotherapy treatments and stratify patients for more suitable targeted therapies. These efforts have identified several molecular markers of prognostic value that have been validated as biomarkers, such as BRCA and KRAS mutations, or are currently under investigation in clinical trials, such as CD8 T cells, immune checkpoint inhibitors and progesterone receptor. Recent advancements in biomarker research have also revealed new targets that have expanded treatment options, introducing poly (ADP-ribose) polymerase (PARP) inhibitors, anti-angiogenic agents, inhibitors targeting signaling pathways, and immunotherapy to improve maintenance therapies or enhance first-line therapy. This review presents a summary of current biomarkers, in clinical use or under evaluation, demonstrating a potential to inform on patient selection for treatment efficacy and predict response to EOC therapies, with particular focus on the serous subtypes, including high-grade and low-grade serous carcinomas.

Keywords: BRCA; PARP inhibitors; anti-angiogenic therapy; high-grade serous; hormone therapy; immunotherapy; long-term survival; low-grade serous; markers; targeted therapy.