Targeting autophagy as treatment for Receptor Tyrosine Kinase-amplified cancers

• Applicant: Silvia Vega-Rubin-de-Celis, Ph.D.
• Subject Area: Cell Biology ; Biochemistry
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405351100

Breast cancer is the most common cancer in women and about 20% of them have amplifications in HER2, which correlates with a more aggressive disease. HER2 is a receptor tyrosine kinase (RTK) of the epidermal growth factor (EGF) receptor family, and it regulates cell growth and survival. Targeted therapies with HER2 inhibitors are currently applied in clinical medicine but not all HER2+ breast cancer patients respond to these therapies, most of them develop resistance over time and in the metastatic setting the benefits of these therapies are very limited. Therefore, there is a need for finding more efficient alternative treatments. We discovered that autophagy is inhibited by HER2 and that autophagy inducers might be a potential treatment on these kind of cancers. Autophagy is an intracellular degradation process in which the engulfment of cytoplasmic and organelle components by double-membraned vesicles, autophagosomes, leads to their degradation in the lysosome. Autophagy is an evolutionary conserved pathway implicated in many physiological and pathological conditions, including protection against diseases, such as cancer. Autophagy de-regulation has been shown in several types of cancer, and it is now clear that it plays a role in both tumor formation and progression. Therefore, we aim to define new mechanisms whereby RTKs regulates autophagy to further develop therapeutic options using targeted autophagic vulnerabilities

• DFG Programme: Research Grants