PSMA-targeted Therapies Work Best in Tumors with Mutations in DNA Repair Genes, Study Suggests

PSMA-targeted Therapies Work Best in Tumors with Mutations in DNA Repair Genes, Study Suggests
Tumors with large numbers of prostate cancer cells with mutations in DNA repair genes are easier to target using prostate-specific membrane antigen (PSMA) therapies, and patients with these tumors are more likely to respond to this potential treatment's use, a study found. Results from the study, "Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer," were published in European Urology. PSMA is a membrane protein often found at very high levels on the surface of prostate cancer cells, especially among those forming castration-resistant prostate cancer (CRPC) tumors, an aggressive form of the disease that no longer responds to hormone therapy. For that reason, PSMA has become a promising target of researchers working to develop a new class of medications that combine an anti-PSMA antibody with a radioactive compound. Such medications, like LuPSMA-617, use the anti-PSMA antibody to specifically spot and deliver the radioactive compound to prostate cancer cells producing PSMA in large amounts. But this type of targeted radiation therapy does not work for all patients, and the rates of those failing to respond have amounted to about 30% in studies. Between 30% to 60% of patients with metastatic CRPC (mCRPC) treated with these therapies, however, have reported reductions of more than 50% in PSA levels (a biomarker of prostate cancer). "One potential explanation for these discrepancies is heterogeneity of PSMA expression," researchers in this study wrote. "However, the extent of, implications of, and mechanisms underlying this phenomenon remain poorly understood," mostly because prior studies used antibodies that target the intracellular part of PSMA, which has no clinical value for estimating PSMA levels. A team of
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