The cancer cell adhesome connects the cell with both the surrounding extracellular matrix (ECM) and the cell membrane with the cytoplasmic and nuclear matrix. It is well accepted that the cancer cell adhesome fundamentally impacts on the response to anticancer therapies. Our preliminary data outlines that growth in three-dimensional ECM and ECM stiffness are key determinants for DNA repair efficacy as well as chromatin organization and flexibility. The aim of this project is identifying the underlying mechanisms how the adhesome/Chromatin/DNA repair machinery controls cancer cell resistance to (radio)therapy and facilitates the development of acquired resistance in head and neck squamous cell carcinomas.
This project will unravel how adhesome, chromatin and DNA repair are mechanistically intertwined and identify new targets for combined cancer therapy.