Although prostate cancer is the type of cancer most commonly survived by men in the United States, it remains the second most common cause of death from cancer, largely owing to metastatic disease. Patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed on standard-of-care therapies have few options and a poor prognosis. Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein that is commonly expressed in prostate cancer. Expression is limited on extra-prostatic tissues other than the salivary glands, lacrimal glands, duodenal epithelium, Kupffer cells, and renal tubules. PSMA-directed theranostics has emerged to exploit the specificity of PSMA for prostate cancer cells and has demonstrated promising results in the clinic. Radionuclides linked to PSMA inhibitors/binders have resulted in US Food and Drug Administration (FDA) approval of 2 radiodiagnostics for PSMA-directed positron emission tomography/computed tomography. In addition, these radionuclides have led to the development of lutetium Lu 177PSMA-617 therapy, which is currently under priority FDA review. Multiple novel PSMA-targeted modalities have been developed and are currently under clinical investigation, including ligand-drug and cellular immune therapies. In this review, we discuss the development of PSMA-directed theranostics, along with its clinical implications, limitations, and future directions.
Clinical advances in hematology & oncology : H&O. 2022 Apr [Epub]
Nathan M Hawkey, Alton O Sartor, Michael J Morris, Andrew J Armstrong
Department of Medicine, Duke University School of Medicine, Division of Medical Oncology, Durham, North Carolina., Tulane Cancer Center, Division of Genitourinary Oncology, New Orleans, Louisiana., Memorial Sloan Kettering Cancer Center, Genitourinary Oncology Service, New York, New York.