Abstract & Overview
Ovarian cancer is one of the most aggressive and lethal gynecological malignancies, with the disease progressing to advanced stages with high recurrence rates, primarily due to the lack of effective early detection methods. High-grade serous ovarian cancer (HGSC), the most common subtype, is characterized by rapid metastasis and genomic instability, often driven by TP53 and BRCA mutations. Standard treatment includes cytoreductive surgery followed by platinum-based chemotherapy, with emerging targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenic agents improving outcomes in select patient populations. However, treatment resistance and tumor recurrence remain significant challenges. This review explores the molecular mechanisms underlying ovarian cancer progression, with a focus on clonal evolution, cancer stem cells (CSCs), and circulating tumor cells (CTCs), which contribute to tumor heterogeneity, chemoresistance, and metastasis. The tumor microenvironment (TME) plays a crucial role in immune evasion, further complicating treatment. Liquid biopsy technologies offer new avenues for real-time monitoring of CTCs and CSC-related biomarkers, such as aldehyde dehydrogenase 1A1 (ALDH1A1), enabling personalized treatment strategies. Novel therapeutic approaches, including PARP inhibitors combined with immune checkpoint inhibitors, epigenetic therapies, and chimeric antigen receptor (CAR)-T cell therapy targeting CSCs, are under investigation to overcome resistance and improve clinical outcomes. Future research integrating molecular profiling, liquid biopsy technologies, and combination therapies holds promise for improving survival and quality of life in patients with ovarian cancer.