Evolving Castration Resistance and Prostate Specific Membrane Antigen Expression: Implications for Patient Management

SIMPLE SUMMARY: This review is a summary of recent findings on the role of prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer (mCRPC) and how they can be implemented into patient management. The multiple aspects, interactions and functions of PSMA expression should be considered with regard to diagnosis and treatment. Approval of (177)Lu-PSMA radioligand therapy (PSMA-RLT) by the FDA is impending and might lead to broader indications for application than third-line therapy of mCRPC. Earlier use of PSMA-RLT and combinatorial approaches with other novel agents are the promising future of mCRPC management. ABSTRACT: Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease, despite multiple novel treatment options. The role of prostate-specific membrane antigen (PSMA) in the process of mCRPC development has long been underestimated. During the last years, a new understanding of the underlying molecular mechanisms of rising PSMA expression and its association with disease progression has emerged. Accurate understanding of these complex interactions is indispensable for a precise diagnostic process and ultimately successful treatment of advanced prostate cancer. The combination of different novel therapeutics such as androgen deprivation agents, 177LU-PSMA radioligand therapy and PARP inhibitors promises a new kind of efficacy. In this review, we summarize the current knowledge about the most relevant molecular mechanisms around PSMA in mCRPC development and how they can be implemented in mCRPC management.