Considering the potential for gene-based therapy in prostate cancer

Abstract

Therapeutic gene manipulation has been at the forefront of popular scientific discussion and basic and clinical research for decades. Basic and clinical research applications of CRISPR–Cas9-based technologies and ongoing clinical trials in this area have demonstrated the potential of genome editing to cure human disease. Evaluation of research and clinical trials in gene therapy reveals a concentration of activity in prostate cancer research and practice. Multiple aspects of prostate cancer care — including anatomical considerations that enable direct tumour injections and sampling, the availability of preclinical immune-competent models and the delineation of tumour-related antigens that might provide targets for an induced immune system — make gene therapy an appealing treatment option for this common malignancy. Vaccine-based therapies that induce an immune response and new technologies exploiting CRISPR–Cas9-assisted approaches, including chimeric antigen receptor (CAR) T cell therapies, are very promising and are currently under investigation both in the laboratory and in the clinic. Although laboratory and preclinical advances have, thus far, not led to oncologically relevant outcomes in the clinic, future studies offer great promise for gene therapy to become established in prostate cancer care. Prostate cancer lends itself to gene therapies, and multiple aspects of prostate cancer care make gene therapy an appealing treatment option for this common malignancy. Although laboratory and preclinical advances have not yet resulted in oncologically relevant outcomes in the clinic, future studies offer great promise for gene therapy to become established in prostate cancer treatment. Prostate cancer gene therapy research and clinical trials established a foundation and path forwards for future advances in the field. Gene therapy strategies with potential applications in patients with prostate cancer include direct injection into a prostate tumour or systemic administration (vaccination). Preclinical data on both strategies are promising, but large clinical trials have failed to demonstrate oncological benefit in patients. Further work, for example, modified vaccination strategies and the use of the CRISPR–Cas9 system, offers hope for future applications of gene therapy approaches in humans.