Abstract
Simple SummaryThis 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 177Lu-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.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.
Highlights
Prostate cancer (PCA) is the most common male cancer with approximately 60,000 new cases in Germany each year [1]
Even if the protein with its enzymatic functions is well characterized, there is no known natural ligand to prostate-specific membrane antigen (PSMA) to date, there have been countless studies which attempted to define the optimal binding motif [72,73,74,75]. Regardless of this lack in knowledge, its internalization is effectively used in PSMA radioligand therapy (PSMA-RLT), where a radio-labeled ligand travels into the cell via PSMA internalization and induces double-strand breaks through local radiation [76], as well as in PSMA PET imaging
As we showed recently in such advanced heavily treated disease stages, there might be underlying molecular mechanisms of tumor dedifferentiation towards neuroendocrine phenotypes that have not yet reached a measurable stage using the common biomarkers, but may escape advanced heavily treated disease stages, there might be underlying molecular mechanisms of tumor dedifferentiation towards neuroendocrine phenotypes that have not yet reached a measurable stage using the common biomarkers, but may escape adenocarcinomafocused treatment [115]
Summary
Prostate cancer (PCA) is the most common male cancer with approximately 60,000 new cases in Germany each year [1]. Androgen deprivation therapy (ADT) is the usually the first line of treatment for those cases [5]. PSMA seems to play a major role in the progression to castration resistance, which is potentially induced or promoted by androgen deprivation therapy (ADT) [15]. Little was known about the biological function of PSMA in cancer, nor about its role in the progression of prostate cancer into the stage of castration resistance and eventually neuroendocrine PCA, until very recently. We will dissect the role of PSMA in evolving castration resistance and why this makes it a valuable therapeutic target in late mCRPC, and a valid and safe biomarker for imaging and disease staging [24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
