Grant to fund use of kinase test in HER2-positive breast cancer

Chapel Hill, NC – Susan G. Komen for the Cure® has awarded a grant of almost $900,000 to Lisa A. Carey, MD, and Gary Johnson, PhD, to research clinical applications for the first broad-based test for protein kinase activation and response to inhibitory drugs in HER2-positive breast cancer.

Kinases are proteins expressed in human tissues that play a key role in cell growth, particularly in cancer. Of the 518 known human kinases, about 400 are expressed in cancers, but which ones and how many are actually active in tumors has been difficult to measure. Tremendous efforts have been made to develop kinase inhibitors as cancer treatments, which have resulted in key drugs such as Herceptin®, Tykerb®, and Gleevec®. However, in spite of the effectiveness of this class of cancer drugs, most cancers eventually become resistant.

Johnson, who is the Kenan Distinguished Professor and chair of the department of pharmacology in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center, worked with his team to develop a test that can measure both the presence and activity of 60-70 percent of all kinases simultaneously, allowing investigators to see how cancers evade treatment with kinase inhibitors so that they can combine drugs to block resistance.

Carey, who is Preyer Distinguished Professor of Breast Cancer Research and medical director of the UNC Breast Center, says, “HER2 positive breast cancers comprises about 20 percent of all breast cancers. Several HER2-targeted drugs are in clinical use and many more are in development. But we don’t know who needs which targeted drug and why, who needs dual HER2-targeted therapy, and what other strategies might be needed to best treat HER2-positive breast cancer.”

The team will use the test developed in Johnson’s lab as part of a clinical trial led by Keith Amos, MD, assistant professor of surgical oncology, to understand the kinome activation state before and after treatment with kinome-targeted drugs to determine how and why the tumors “reprogram” in response to various HER2-targeted therapies. Their goal is to define the best combinations of therapies and to develop selection strategies for individual patients.

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