Genetic target could help treat aggressive prostate Cancer

Researchers at the University of Michigan Comprehensive Cancer Center, Ann Arbor, have identified a potential target to treat an aggressive type of prostate cancer.

The target, a gene called SPINK1, could be to prostate cancer what HER2 has become for breast cancer, according to the Michigan team, whose research is published in Science Translational Medicine (2011; 3:72ra17). SPINK1 is associated with a more aggressive form of prostate cancer. It can be detected in the urine of prostate cancer patients, making it an easy test for urologists to perform routinely.

SPINK1 occurs in only about 10% of prostate cancers. But the gene is an ideal target for a monoclonal antibody, the same type of drug as trastuzumab (Herceptin), which is aimed at HER2 and has dramatically improved treatment for an aggressive type of breast cancer.

"Since SPINK1 can be made on the surface of cells, it attracted our attention as a therapeutic target," said senior author Arul Chinnaiyan, MD, PhD. "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."

Using mice, the team first tested SPINK1. They then tested cetuximab (Erbitux). Tumors treated with the SPINK1 antibody shrunk 60%, while tumors treated with cetuximab shrunk 40%. By combining the two drugs, tumors were 74% smaller. The effect was seen only in tumors that expressed SPINK1 and was not seen in tumors that did not express the gene.

"About 10% of prostate cancer patients are SPINK1-positive, and strategies to block SPINK1 signaling may have utility in this subset of patients," said first author Bushra Ateeq. "These studies should stimulate the development of antibody-based therapies against SPINK1 or targeting of EGFR in SPINK1-positive cancer patients."