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The inhibition of sorting proteins as a therapeutic avenue in HER2 positive breast cancer

Periodic Reporting for period 1 - SaveHER (The inhibition of sorting proteins as a therapeutic avenue in HER2 positive breast cancer)

Periodo di rendicontazione: 2018-03-01 al 2019-08-31

Our ERC PoC project was entitled “SaveHER: The inhibition of sorting proteins as a therapeutic avenue in HER2 positive breast cancer”. HER2-positive breast cancers are extremely aggressive and, unfortunately, the prognosis for patients suffering from this disease is poor. This is mainly because almost a quarter of patients receiving the main treatment for this disease (anti-HER2 antibodies) eventually develop resistance and the cancer continues to grow. Therefore, understanding the biology of HER2-positive breast cancers is extremely important not only to find new therapies to improve the prospect of the hundreds of thousands of patients affected worldwide but also to counteract the devastating socioeconomic impact of this disease.
HER2 is a receptor that resides on the cell’s surface and is in prime position to sense and interpret signals from the cell’s environment to keep the cells alive and functioning. In HER2-positive breast cancer, there is an amplification of HER2 on the cancer cell’s surface, which means that the volume of the survival signal is turned up and cancer cells continue to divide and grow. In our laboratory, we wanted to find an alternative way to break the HER2 communication lines between cancer cells and their environment. For this purpose, we targeted a sorting protein using antibodies. We first tested the effects of a commercially available antibody, customised for in vivo use, on breast cancer tumour-cell growth and we saw a significant reduction in tumour size. These data suggest that we can target sorting to inhibit cancer cell proliferation. To find a promising therapy to do exactly that, we also collaborated with chemists to generate and test a series of new binding molecules for our protein of interest that could later be developed into more efficient antibodies suitable for human use.