Abstract
Simple SummaryProstate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in prostate cancer and correlates with the aggressiveness of the disease. PSMA is a promising target for imaging and therapeutics in prostate cancer patients validated in prospective trials. However, the role of PSMA in prostate cancer progression is poorly understood. In this review, we discuss the biology and scientific rationale behind the use of PSMA and other targets in the detection and theranostics of metastatic prostate cancer.Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.
Highlights
Prostate cancer is the second most commonly diagnosed cancer in men and the sixth leading cause of cancer-related deaths among men worldwide incidence and mortality of prostate cancer vary depending on the country [1]
We will critically discuss the scientific rationale behind the use of Prostate-specific membrane antigen (PSMA)-directed molecular imaging and therapeutics and compare it to other potential targets evaluated in imaging of metastatic prostate cancer to guide management
PSMA is a multifunctional protein expressed in some healthy tissues, the most significant expression levels are found in humans in the prostatic epithelium
Summary
Prostate cancer is the second most commonly diagnosed cancer in men and the sixth leading cause of cancer-related deaths among men worldwide incidence and mortality of prostate cancer vary depending on the country [1]. The prognosis for localized prostate cancer is good, with 5-year survival rates above 90%, recurrence can occur after radical therapy, and many patients have metastases at the time of primary diagnosis [2]. Conventional 99m Tc-bone scintigraphy and computed tomography (CT) showed limited diagnostic accuracy to detect and localize disease or treatment response in many cases. They are insensitive in the event of biochemical relapse with a rising prostate-specific antigen (PSA) after radical treatment, presenting an unmet need for better methods. We will critically discuss the scientific rationale behind the use of PSMA-directed molecular imaging and therapeutics and compare it to other potential targets evaluated in imaging of metastatic prostate cancer to guide management
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