Emerging molecular targets in gynaecologic cancers: clinical implications for personalized therapy

Gynaecologic malignancies, such as ovarian, cervical, endometrial, vulvar, and vaginal cancers, are a significant health burden in the world, characterised by significant heterogeneity in their mode of expression on the molecular scale, high rates of recurrence, and low rates of sustained response to standard treatment. Recent progress in cancer genomics has essentially redefined the nature of these diseases, discovering multifaceted genetic, epigenetic, and tumour microenvironment-based processes that regulate tumour progression, therapeutic response, and resistance. This review summarises the existing knowledge about the molecular pathogenesis of gynaecologic cancers, including the essential oncogenic pathways, such as PI3K/AKT /mTOR pathways, malfunctioning DNA damage repair, angiogenesis, hormone receptors, and tumour immune interactions. Efforts are also analysed in areas of clinical integration of biomarker-driven targeted therapies, including poly(ADP-ribose) polymerase inhibitors, anti-angiogenic agents, immune checkpoint inhibitors, and emerging antibody drug conjugates, highlighting the areas of progress and current shortcomings. Primary and acquired resistance mechanisms, such as tumour microenvironment-mediated adaptations, are also critically considered together with new approaches to overcome therapeutic resistance using rational combination and treatment sequencing. We also see how the role of molecular biomarkers, companion diagnostics, genomic profiling, and liquid biopsy technologies is growing in allowing precision oncology, but ethical, economic, and access-associated limitations limit equitable application. All this review indicates the redefinition of gynaecologic cancer therapy by molecularly informed therapeutic approaches and a translational roadmap towards sustainably achieved biomarker-driven clinical benefit.