Promising treatment for invasive Breast Cancer

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.
The team led by Andreas Plückthun, Director of the Department of Biochemistry at the University of Zurich, involving postdoc Rastik Tamaskovic and PhD student Martin Schwill, has now found out why these antibodies merely slow tumor growth rather than killing off the cancer cells. 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 Andreas Plückthun explains the mechanism, which has been understood in detail for the first time.
The UZH scientists have now discovered an astonishingly effective solution to switch off all signals emanating from HER2 in the cancer cells at the same time. They have designed a protein compound that binds itself simultaneously to two HER2 receptors in a targeted manner and changes their spatial structure. This "receptor bending" prevents any growth signals from being transmitted into the cell interior, and the cancer cells die off. Another advantage is the very selective effect of the substance, which ensures that the cancer cells are killed off efficiently but healthy body cells remain unharmed.