EGFR-TARGETEd THERAPy ANd RESISTANCE

The management of non-small cell lung cancer is undergoing a paradigm shift from empirically-selected treatment to personalised therapy, based on the clinical characteristics of patients and the histological and molecular features of their tumours. This has been driven by the identification of oncogenic ‘drivers’ responsible for cancer cell growth and survival, and the development of specific therapy targeting these. The pivotal discovery was the identification of mutations in the epidermal growth factor receptor and recognition of their exquisite sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors. defining this molecular cohort and instituting targeted therapy has led to significantly improved clinical outcomes over empirical chemotherapy. However, the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors therapy appears universal, and strategies to delay or overcome the emergence of this resistance remain to be defined. Figure 1: The EGFR pathway and potential strategies to target this pathway. Ligand binding to EGFR induces conformational changes that result in the homo or hetero-dimerisation of the receptor and its subsequent autophosphorylation and downstream signalling.