Clinical implications of mismatch repair deficiency in prostate cancer

What is it about?

Immune checkpoint blockade hold promise in the treatment of solid tumors, but is not yet been approved for use in advanced prostate cancer. This is largely due to the relatively modest response in clinical trials in unselected patients and the lack of available biomarkers to determine clinical benefit. Germline and somatic mismatch repair gene deficiencies are more prevalent than previously thought. An early signal suggests that patients with deficiency in mismatch repair may respond well to immunotherapy. Both germline and somatic genetic testing are recommended, yet questions remain on the best modality for testing. Expanded panels, such as next generation sequencing may increase the sensitivity without compromising specificity. Future studies are needed to explore predictors of response to immunotherapy.The drivers of variable response is largely unknown, and a mature understanding of the mechanisms of resistance in dMMR tumors may help to more precisely inform use of immunotherapy in prostate cancer.

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