Scientists at Cold Spring Harbor Laboratory (CSHL) today report a discovery that they hope will lead to the development of a powerful new way of treating an aggressive form of breast cancer.
In a paper appearing online today in Nature Chemical Biology
a multi-institution team led by CSHL Professor Nicholas Tonks
reports that it has found a means of inhibiting another protein, called PTP1B, whose expression is also upregulated in HER2-positive breast cancer. They show that PTP1B plays a critical role in the development of tumors in which HER2 signaling is aberrant. Therefore, PTP1B may be a therapeutic target through which to treat the disease.
When they treated mice modeling HER2-positive breast cancer with a drug candidate called MSI-1436 (also called trodusquemine), Tonks and colleagues not only inhibited signaling by PTP1B, but also signaling by HER2 proteins.
“The result was an extensive inhibition of tumor growth and prevention of metastasis to the lung in HER2-positive animal models of breast cancer,” notes Navasona Krishnan, Ph.D., a postdoctoral investigator in the Tonks lab who performed many of the experiments and is lead author on the paper reporting the results.
Dr. Tonks discovered PTP1B some 25 years ago. It is an enzyme — one in a “superfamily” of 105 called protein tyrosine phosphatases (PTPs) -- that perform the essential biochemical task of removing phosphate groups from amino acids called tyrosines in other proteins. Adding and removing phosphates is one of the principal means by which signals are sent among proteins.
Source: Cold Spring Harbor Laboratories