New Cancer Drugs May Target Tyrosine Phosphatases

Cancer researchers have identified genes from patients with colon cancer involved in synthesis of tyrosine phosphatases that might prove to be targets of choice for new anti-cancer drugs.

Investigators at Johns Hopkins University (Baltimore, MD, USA) performed mutational analysis on the tyrosine phosphatase gene superfamily in human cancers. They identified 83 somatic mutations in six tyrosine phosphatases, affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered tyrosine phosphatase were examined by biochemical techniques and found to reduce phosphatase activity. These results were published in the May 21, 2004, issue of Science.
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"What makes this discovery significant is that we have found mutations that directly affect cancer development,” explained senior author Dr. Victor Velculescu, an assistant professor at the Johns Hopkins University Kimmel Cancer Center. "Most gene discoveries today focus on finding increased or decreased activity of a gene that may not affect cancer progression, akin to passengers on a bus that cannot control the bus's speed or direction. What we have found are the brakes of the bus.”



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