Tumor-specific combinations of oncogenic mutations often free cancer cells from their reliance on growth factors. One important example comprises the epidermal growth factor receptor (EGFR) and its kin, HER2. In tumors, both EGFR and HER2 frequently display overexpression, internal deletions and point mutations. Accordingly, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) specific to these receptors have been approved for clinical applications. My lecture will introduce EGFR and HER2 in the context of a signaling network comprising two additional receptors, HER3 and HER4, and 11 growth factors, all sharing an EGF-like structure and binding to HER family members.
The principles of network biology, such as rewiring, robustness and pathway redundancy, translate to short–term responses to oncology drugs. In other words, patients treated with drugs intercepting EGFR or HER2 often develop resistance due to emergence of compensatory mechanisms. My lecture will exemplify these principles in context of several relatively hard to treat tumors. The tumors I will discuss include breast cancers, both HER2-enriched and triple-negative, ovarian cancer and advanced non-small cell lung tumors that acquired resistance to EGFR’s TKIs.
