New DARPins Appear to Shut Off All HER2 Signals in HER2-Positive Breast Cancer Cells

In Switzerland alone, more than 5,700 women are diagnosed with breast cancer each year, and almost 1,400 of those affected die of the disease. In many very invasive forms of breast cancer, the cells have too much of the receptor HER2 on their surface. This leads to uncontrolled growth of the cells. Various antibodies such as trastuzumab and pertuzumab, which recognize the HER2 receptor, have been used in breast cancer therapy for many years now. However, these antibodies do not kill off the cancer cells. Instead, they render them dormant, and the cancer cells can become active again at any time. In an open-access article published online on June 3, 2016 in Nature Communications, a team led by Andreas Plückthun, Ph.D., Director of the Department of Biochemistry at the University of Zurich, involving postdoc Rastik Tamaskovic and Ph.D. student Martin Schwill, reported finding out why these antibodies merely slow tumor growth rather than killing off the cancer cells. The article is titled “Intermolecular Biparatopic Trapping of ErbB2 Prevents Compensatory Activation of PI3K/AKT via RAS–p110 Crosstalk.” The receptor HER2 uses several signaling pathways at the same time to inform the cell that it should grow and divide. But, the antibodies available thus far, only block one of those signaling pathways, while the others remain active. The most important of these open paths leads through the central hub called RAS. "It is this protein that is responsible for reactivating the growth signal emitted by the HER2 receptor. The antibodies lose effect and the cancer cells continue to proliferate." This is how Dr. Plückthun explains the mechanism, which has been understood in detail for the first time.
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