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Considering the potential for gene-based therapy in prostate cancer

Nature Reviews Urology volume 18, pages 170–184 (2021)Cite this article

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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.

Key points

  • 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.

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Fig. 1: Gene therapy treatment approaches in humans: direct tumour injection and vaccine-based systemic injection.
Fig. 2: CRISPR–Cas9 technology and prostate cancer treatment.

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Acknowledgements

This work was supported by MD Anderson NCI Prostate Cancer SPORE Grant P50 CA140388 and the NCI Cancer Center Support Grant P30 CA16672.

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  1. These authors contributed equally: Justin R. Gregg, Timothy C. Thompson.

Authors and Affiliations

  1. Department of Urology and Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Justin R. Gregg

  2. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Timothy C. Thompson

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Both authors researched data for the article, made substantial contributions to the discussion of the content and wrote, reviewed and edited the manuscript before submission.

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Correspondence to Justin R. Gregg or Timothy C. Thompson.

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Parts of the discussion in this article involve data relevant to intellectual property that has been licensed by Baylor College of Medicine to Progression Therapeutics, Inc., a private biotechnology start-up company. T.C.T. is an inventor of record on patents that are included in this licensing agreement. J.R.G. declares no competing interests.

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Gregg, J.R., Thompson, T.C. Considering the potential for gene-based therapy in prostate cancer. Nat Rev Urol 18, 170–184 (2021). https://doi.org/10.1038/s41585-021-00431-x

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