New Generation Genetic and Immunological Approaches in Gynecological Oncology

Gynecologic malignancies comprising ovarian, endometrial, cervical, vulvar, and vaginal cancers remain major causes of cancer-related mortality in women worldwide. Despite advances in surgery and systemic chemotherapy, recurrence, drug resistance, and limited survival persist in advanced disease. The emergence of immunotherapy and genetic therapy has fundamentally transformed therapeutic strategies, leveraging immune modulation and genomic engineering to achieve durable responses. This review synthesizes recent evidence (2023-2025) on novel immunologic and genetic therapeutic approaches in gynecologic oncology, emphasizing translational mechanisms, clinical trial outcomes, and future directions in precision medicine. A comprehensive literature analysis was performed focusing on checkpoint inhibitors, adoptive cell therapy (TILs, CAR-T/NK), therapeutic vaccines, gene-editing systems (CRISPR/Cas9), RNA-based therapeutics, and integrative omics-guided strategies. Ongoing phase II–III clinical trials were also evaluated. Checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 significantly improved survival in mismatch repair–deficient endometrial and recurrent cervical cancers. Combination regimens integrating ICIs with PARP inhibitors or angiogenesis blockade show synergistic potential in ovarian carcinoma. Adoptive cell therapies including tumor-infiltrating lymphocytes and CAR-engineered cells achieved durable responses in refractory cases. Genetic therapy has advanced through CRISPR-mediated T-cell modification, BRCA gene correction, and RNA interference against oncogenic pathways. Parallel progress in AI-driven neoantigen prediction, single-cell transcriptomics, and multi-omics profiling is refining patient selection and response prediction. However, limitations persist, including immune resistance, off-target genetic effects, high costs, and accessibility disparities. Gynecologic oncology is entering an immunogenetic era where immune checkpoint modulation and genomic editing converge to redefine treatment paradigms. Integrating molecular diagnostics, AI-guided personalization, and combinatorial immunogenetic regimens holds promise for transforming advanced gynecologic malignancies into manageable diseases. Ongoing global trials will determine the scalability and equity of these innovations in clinical practice.