Cancer therapy target: the epidermal growth factor receptor

Usha Padmanabhan

Epidermal growth factor receptor (EGFR) signaling plays an essential role in cell proliferation, survival, and migration. EGFR is a transmembrane protein whose extra cellular domain binds to its physiological ligand EGF and its intracellular domain possesses an intrinsic kinase activity which leads to transcription activation via downstream signalling pathways. Mutations in EGFR which lead to ligand independent and/or constitutive activation of EGFR have been implicated in several cancers such as non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head & neck (SCHNN), colorectal cancer (CRC), and tumors of the ovary, cervix, bladder, esophagus, stomach, brain, endometrium, breast, and liver and provide a basis for targeted therapy. This review summarizes the structure of EGFR1 and structure-function correlation of EGFR mutations characterized in neoplastic tissue and the pharmaceutical drugs that have been developed to target different domains of EGFR1. The use of these drugs in India and their impact on therapy has also been discussed. The clinical data has been obtained from those reported in indexed journals. While the data may not be comprehensive, they nonetheless emphasize the importance of mutational analyses of EGFR1 prior to the use of EGFR1 targeted therapy in India for better management of the disease.

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