This interesting study coming from the renowned lab of Johann de Bono at the Institute for Cancer Research in the U.K. should help us understand why some patients may respond well to the promising PSMA-based therapeutics, like Lutetium 177-PSMA, and others may not.
Through analysis of prostate cancer samples, the authors report that the presence of prostate-specific membrane antigen (PSMA) is extremely variable both within one patient and between different patients. This may limit the usefulness of PSMA scans and PSMA-targeted therapies. They show for the first time that prostate cancers with defective DNA repair (e.g., BRCA, ATM mutations) produce more PSMA and so may respond better to PSMA-targeting treatments. The variability in PSMA production by prostate cancer cells was seen in both castrate sensitive and castrate resistant tumors.
The full abstract is available here: https://www.ncbi.nlm.nih.gov/pubmed/31345636