A potential candidate for radiopharmaceutical therapy: GPNMB
Readers of Discovery are likely familiar with PSMA, an enzyme that sits on the surface of prostate cancer cells. PSMA can be targeted for imaging with a radioactive tracer, and for treatment with a radionuclide – a radiation-emitting particle that can kill individual prostate cancer cells throughout the body. Some forms of kidney cancer may have a similarly good target: Glycoprotein NMB (GPNMB). Like PSMA, this is a protein that sits on the surface of cells, and scientist Kaushal Asrani, M.B.B.S., Ph.D., aims to use this for detection and treatment of certain renal tumors: aggressive cancers that are driven by specific proteins called MiT and TFE.
“These proteins are known to promote renal tumors in translocation renal cell carcinomas (tRCC) and tuberous sclerosis complex (TSC),” says Asrani. “However, despite considerable advances in our understanding of MiT/TFE biology, we have not identified the mechanisms by which they drive kidney tumor formation, or leveraged this knowledge for their detection or treatment.”
There are no diagnostic biomarkers for tRCC, which can affect children, and there is no long-lasting treatment for TSC. However: In a recent study, published in the Journal of Pathology, https://pubmed.ncbi.nlm.nih.gov/35072947/ “we showed that GPNMB expression is highly increased in tRCC and TSC, distinguishing them from other types of kidney tumors.”
In collaboration with George Sgouros, Ph.D., Director of the Radiological Physics Division, Asrani will determine whether “GPNMB promotes renal tumor formation in tRCC and TSC, and whether cell-surface GPNMB can be targeted for alpha-particle radiopharmaceutical therapy.” And if this proves to be the case: “We will create a highly potent and specific alpha-particle emitter, and evaluate its therapeutic potential in kidney tumor models of tRCC and TSC.”