A potential target to treat an aggressive form of prostate cancer was identified by researchers at the University of Michigan Comprehensive Cancer Center. SPINK1 gene, could be to prostate cancer.
Like HER2, SPINK1 occurs in only a small subset of prostate cancers about 10 percent. But the gene is an ideal target for a monoclonal antibody, the same type of drug as Herceptin, which is aimed at HER2 and has dramatically improved treatment for this aggressive type of breast cancer.
Advertisement"Since SPINK1 can be made on the surface of cells, it attracted our attention as a therapeutic target. Here we show that a 'blocking' antibody to SPINK1 could slow the growth of prostate tumors in mice that were positive for the SPINK protein," says study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and a Howard Hughes Medical Institute Investigator.
The study appears in the March 2 issue of Science Translational Medicine.
The researchers additionally found that SPINK1 can bind to a receptor called EGFR. They tested a drug that blocks EGFR, cetuximab, which is already approved by the U.S. Food and Drug Administration, and found that this also reduced the cancerous effects of SPINK1.
Using mice, researchers first tested a monoclonal antibody a type of targeted treatment designed to go after a specific molecule (in this case, SPINK1). They then tested cetuximab. Tumors treated with the SPINK1 antibody shrunk 60 percent, while tumors treated with cetuximab shrunk 40 percent. By combining the two drugs, tumors were 74 percent smaller.
The effect was seen only in tumors that expressed SPINK1 and was not seen in tumors that did not express SPINK1.
Previous studies that looked at cetuximab for metastatic prostate cancer have been disappointing, with only 8 percent of patients showing some benefit. The researchers suggest that the poor results may be because the treatment is appropriate only for patients with SPINK1-positive tumors.