Gene Therapies for Cancer: Strategies, Challenges and Successes

Abstract

Gene therapy, which involves replacement of a defective gene with a functional, healthy copy of that gene, is a potentially beneficial cancer treatment approach particularly over chemotherapy, which often lacks selectivity and can cause non-specific toxicity. Despite significant progress pre-clinically with respect to both enhanced targeting and expression in a tumor-selective manner several hurdles still prevent success in the clinic, including non-specific expression, low-efficiency delivery and biosafety. Various innovative genetic approaches are under development to reconstruct vectors/transgenes to make them safer and more effective. Utilizing cutting-edge delivery technologies, gene expression can now be targeted in a tissue- and organ-specific manner. With these advances, gene therapy is poised to become amenable for routine cancer therapy with potential to elevate this methodology as a first line therapy for neoplastic diseases. This review discusses recent advances in gene therapy and their impact on a pre-clinical and clinical level.

Fig. 1

The timelines and milestones in developing gene therapy approaches: from conception to clinical applications.

Fig. 2

Progression timelines for mda-7/IL-24 development as a therapeutic gene: from “bench to bedside.” After discovery, multiple approaches were used to enhance therapeutic outcome of mda-7/IL-24-mediated gene therapy of cancer.