One of the major challenges of modern molecular biology is to understand how healthy cells transform into malignant, proliferating cells leading to diseases such as cancer and which proteins trigger these aberrant signalling cascades. The ErbB family of receptor tyrosine kinases (RTKs) are pivotal mediators of the signalling network that transmit extracellular signals into the cell and control cell growth, proliferation, differentiation and survival. Excessive ErbB signalling arises from receptor overexpression or mutation and is a hallmark of various cancers. Yet, despite 25 years of in-depth studies of RTK signalling, some aspects remain elusive and deeper understanding of signalling pathways downstream of mutant receptors will likely improve current EGFR-targeted therapies. Hence, the main aim of this proposal is to identify novel players in EGFR signalling as potential novel cancer drug targets. This will be achieved by transferring a novel two-hybrid technique that I have developed during my previous postdoc to the host institution and combining it with their expertise in cancer signalling. I will a) perform interaction screens to identify novel interactors of EGFR and its cancerous variants and b) perform small molecule compound screens to identify drugs that can interfere with interactions that specifically occur with these oncogenic EGFRs. Our ultimate goal is to identify chemical compounds that can be taken further to therapeutic development.
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