Bridging the Gap: Linking Molecular Pathways to Therapeutics in Ovarian Cancer

Introduction Ovarian cancer, a leading cause of cancer-related deaths among women, remains a significant public health challenge due to its late-stage diagnosis and limited therapeutic options. Despite advancements in treatment, traditional chemotherapy regimens, often involving platinum-based drugs, have limited efficacy and can result in severe side effects. This underscores the urgent need for targeted therapies that exploit the underlying molecular pathways driving ovarian cancer progression. This review aims to explore the key genetic, signaling, and clinical pathways involved in ovarian cancer, with a particular focus on those with approved drugs. Methods A comprehensive literature search was conducted using PubMed and Google Scholar to identify relevant studies published between ۲۰۱۵ and ۲۰۲۳. Key search terms included "ovarian cancer", "molecular pathways", "genetic pathways", "therapeutic targets", "targeted therapy", "clinical trials", and "approved drugs". Only articles with full text available were included in the analysis. The retrieved articles were carefully reviewed to extract information on the most significant pathways, their clinical implications, and associated therapeutic advancements. Results Several key molecular pathways have been implicated in the development and progression of ovarian cancer. PI۳K/AKT/mTOR pathway is frequently activated in ovarian cancer, promoting cell survival, proliferation, and angiogenesis,and its activation is linked to aggressive behavior and poor prognosis. Inhibitors of this pathway, such as everolimus and PI۳K inhibitors like alpelisib and ipatrafinib, have shown promising clinical activity. Vascular endothelial growth factor (VEGF) signaling is essential for tumor angiogenesis which is a key characteristic of cancer, and targeting tumors by disrupting their vasculature is a promising anticancer approach. Anti-VEGF antibodies, like bevacizumab and ramucirumab, have become standard of care in the treatment of ovarian cancer. DNA replication and repair are essential for cancer cell survival. PARP enzymes are activated by DNA damage, and the successful introduction of PARP inhibitors has revolutionized the treatment of ovarian cancer, particularly in patients with homologous recombination deficiency (HRD). Olaparib, rucaparib, and niraparib are examples of approved PARP inhibitors. The Wnt pathway plays a crucial role in controlling cell proliferation, differentiation, and migration, as evidenced by its strong influence on cancer stem cell (CSC) self-renewal, epithelial-mesenchymal transition (EMT), invasion, and suppression of tumor immunity. Aberrant activation of this pathway has been observed in ovarian cancer. Targeting the Wnt pathway with small molecule inhibitors, such as porcupine inhibitors and frizzled inhibitors, is an emerging area of research. Conclusion In conclusion, this review highlights the importance of understanding the molecular pathways underlying ovarian cancer for the development of effective targeted therapies. While significant progress has been made, further research is needed to identify additional therapeutic targets and improve treatment outcomes for patients with this devastating disease. By bridging the gap between molecular pathways and therapeutics, we can move closer to personalized medicine for ovarian cancer.

کلیدواژه ها:

Ovarian cancer ، genetic pathways ، signaling pathways ، targeted therapy