Targeting Prostate Specific Membrane Antigens in Renal Cell Carcinoma

WRITTEN BY: Courtney Schaal

Prostate Specific Membrane antigens (PSMA) encoded by the gene FOLH1, and also known as glutamate carboxypeptidase 2, are transmembrane proteins that have had great utility in the molecular imaging of prostate cancer using positron emission tomography (PET) and detecting its presence, as well as being targeted by small molecules with radionuclides, and exploited therapeutically. PSMA is expressed normally in non-malignant prostate epithelial cells, but is well known to be upregulated in prostate tumors. Aside from being expressed in cells of the prostate, PSMA is expressed by endothelial cells including those of the vasculature networks of other solid tumors such as renal cell carcinoma (RCC).

RCC is the most common type of kidney cancer occurring in adults, accounting for nearly 95% of all cases. Patients presenting with localized RCC typically undergo partial or in some cases complete removal of the effected kidney, and have a survival rate of 65-90%. This number decreases dramatically if the disease has advanced and metastasized to other organs. As with many cancers, typically by the time a RCC patient presents in the clinic they have advanced disease. This is largely because RCC tends to be asymptomatic until later stages of progression, so determining markers for early detection would be valuable and potentially life-saving. Two scientists at the James Buchanan Brady Urological Institute and Department of Urology at Johns Hopkins University in Baltimore, Maryland have utilized the fact that PSMA is expressed in the neovasculature of RCC, and used PSMA-targeted PET radio labels to successfully image RCC in their patients, and with greater sensitivity than traditional imaging modalities allowing them to detect metastatic disease in clear cell RCC (ccRCC). Further, Sophia Spatz, a researcher at the Clinic of Urology, University Hospital Bonn in Bonn, Germany, and her colleagues published findings that PSMA was not only expressed in a cohort of 257 RCC patient tumors by histological staining, but the levels of expression correlated with disease stage and grade, as well as overall survival. These findings were further confirmed by RNA expression data from The Cancer Genome Atlas.

These reports lend evidence that PSMA may also have utility in diagnostic imaging and therapeutic targeting in RCC in addition to its more traditional use in prostate cancer. If it could be effectively targeted in RCC, this holds potential to offer a therapeutic intervention even for advanced disease for which there are currently no good treatment options, and to date remains incurable.