ASCO 2021: PSMA-targeted radionuclide therapy for prostate cancer

Prostate-specific membrane antigen (PSMA) is overexpressed in more than 80% of prostate cancer tumors, making it a promising diagnostic and therapeutic target. Given the highly limited expression of PSMA outside of the prostate, precision approaches that specifically target PSMA have been of substantial interest in the field. PSMA-targeted radionuclide therapy combines a PSMA ligand with a radioactive compound that inhibits tumor cell growth and replication through induction of DNA damage. Early data assessing radiolabeled monoclonal antibodies against PSMA demonstrated some efficacy against prostate tumors but were hindered by poor tumor permeability and slow blood clearance. More recent investigations have assessed radiolabeled small molecules that show more promise. Evidence to date highlights radionuclide therapy as an exciting new option for metastatic castration-resistant prostate cancer, an area in which there is a high unmet need for new targeted treatment options. In this deep dive into the latest in PSMA-targeted radionuclide therapy, Karim Fizazi, MD, PhD, Institut Gustave Roussy, and Scott Tagawa, MD, MS, Weill Cornell Medical College, discuss results from the VISION trial of 177Lu-PSMA-617 and a Phase I/II study of 225Ac-J591, as well as the future of PSMA-targeted agents and important unanswered questions.