Dr. Antonarakis on Implications of an MMR Deficiency in Prostate Cancer

Emmanuel S. Antonarakis, MD
Published: Wednesday, Apr 17, 2019



Emmanuel S. Antonarakis, MD, associate professor of oncology, Johns Hopkins University, discusses the clinical implications of an MMR deficiency in patients with prostate cancer.

MMR genes are responsible for Lynch syndrome if inherited, says Antonarakis, but they can also be acquired. These genes include MSH2, MSH6, MLH1, and PMS2. These are the genes that cause hypermutated tumors with hundreds, if not thousands, of mutations. Therapeutically, this is important because in solid tumors, if a patient harbors a MMR deficiency or mutation, they can receive pembrolizumab (Keytruda), a PD-1 inhibitor, which is now FDA approved for solid tumors agnostic of origin as long as the patient has the MMR gene mutation, explains Antonarakis.

Unfortunately, this only represents about 3% to 5% of all advanced prostate cancers, says Antonarakis. Nonetheless, pembrolizumab can be used in this patient population and is included in the guidelines for prostate cancer.
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Emmanuel S. Antonarakis, MD, associate professor of oncology, Johns Hopkins University, discusses the clinical implications of an MMR deficiency in patients with prostate cancer.

MMR genes are responsible for Lynch syndrome if inherited, says Antonarakis, but they can also be acquired. These genes include MSH2, MSH6, MLH1, and PMS2. These are the genes that cause hypermutated tumors with hundreds, if not thousands, of mutations. Therapeutically, this is important because in solid tumors, if a patient harbors a MMR deficiency or mutation, they can receive pembrolizumab (Keytruda), a PD-1 inhibitor, which is now FDA approved for solid tumors agnostic of origin as long as the patient has the MMR gene mutation, explains Antonarakis.

Unfortunately, this only represents about 3% to 5% of all advanced prostate cancers, says Antonarakis. Nonetheless, pembrolizumab can be used in this patient population and is included in the guidelines for prostate cancer.

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