Cancer remains a formidable global health challenge, representing the second leading cause of mortality worldwide. In 2023, there were approximately 18.5 million new cancer cases and over 10 million deaths globally, with projections estimating 30.5 million new cases and 18.6 million deaths annually by 2050. In the US, an estimated 2,114,850 new cases and 626,140 deaths are projected for 2026. Cancer arises from accumulated genetic and epigenetic alterations that progressively transform normal cells into malignant counterparts, with mutations in proto-oncogenes, tumor suppressor genes, and DNA repair machinery as fundamental drivers of carcinogenesis. Gene therapy has emerged as a therapeutic modality that addresses cancer at its genetic core. This review examines the genetic basis of cancer pathogenesis and analyzes contemporary gene delivery platforms viral vectors, bacterial vectors (bactofection), physical methods (microinjection, electroporation, hydroporation, and gene gun), and chemical approaches (lipofection, polymer based systems, and nanoparticles)alongside their advantages, limitations, and clinical applications. Particular emphasis is placed on suicide gene therapy and immunomodulatory approaches, with focused examination of chimeric antigen receptor T cell (CAR-T) therapy as the most clinically advanced gene therapy strategy to date. Recent advances, including expanded regulatory designations for CAR-T therapies targeting solid tumors and next-generation vector platforms, underscore the field's rapid evolution. Despite persistent challenges safety concerns, high costs, and limited efficacy in solid tumors, gene therapy represents a transformative approach that may ultimately achieve durable remissions. We conclude by discussing future directions, including next-generation delivery systems, genome editing technologies such as CRISPR-Cas9 base and prime editing, and strategies to improve accessibility and affordability.
