Abstract
Gynecologic disorders, such as cervical and ovarian tumors, uterine fibroids, and endometriosis, present significant clinical challenges due to frequent recurrence, emerging chemoresistance, and undesirable effects associated with prolonged hormonal treatments. Conventional therapies often fail over time as tumors develop resistance through mechanisms that include the inactivation of tumor suppressor genes, immune evasion, and activation of oncogenic signaling pathways. These limitations underscore the urgent need for more precise and durable therapeutic strategies. Gene- and cell-based therapies have emerged as promising next-generation approaches to address these challenges. CRISPR/Cas9-based editing, RNA-directed regulation, and targeted gene modulation are being employed to silence resistance genes, restore tumor suppressors, and resensitize tumors to platinum (Pt)-based chemotherapy, hormonal therapy, and immunotherapy. Delivery platforms such as receptor-targeted lipid nanoparticles (LNPs) and viral vectors (VVs) enhance tissue specificity and improve therapeutic efficacy. Concurrently, advanced immune cell therapies, including modified natural killer (NK) cells and CAR-T cells, are being designed to eradicate tumor clones that evade standard therapeutic approaches. For benign gynecologic conditions, mesenchymal stem cells (MSCs) demonstrate regenerative potential and may offer an alternative to repeated surgical interventions or prolonged hormonal suppression. This review summarizes recent trends in gene and cell therapies for uterine disorders and gynecologic cancers, with a focus on their potential to enhance therapeutic efficacy, overcome drug resistance, and preserve reproductive health.