Epidermal growth factor receptor (EGFR) mutant kinase (EGFR)

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with intrinsic tyrosine kinase activity that plays a critical role in regulating cell growth and survival (UniProt P00533). Mutations in the EGFR gene, particularly within the kinase domain, lead to constitutive activation of the receptor and are primary drivers in several malignancies, most notably non-small cell lung cancer (NSCLC) (PMID: 29401113). These mutations, such as exon 19 deletions and the L858R point mutation, sensitize the receptor to targeted therapies known as tyrosine kinase inhibitors (TKIs). Over time, tumors often develop secondary resistance mutations, such as T790M or C797S, which necessitate the development of subsequent generations of inhibitors (PMID: 30545547). Therapeutic strategies focus on selectively inhibiting these mutant forms while sparing wild-type EGFR to minimize side effects like skin rash and diarrhea. Understanding the specific mutational profile of a patient tumor is essential for selecting the most effective TKI and monitoring for the emergence of resistance.

Other names

ErbB1HER1Proto-oncogene c-ErbB-1Receptor tyrosine-protein kinase erbB-1

Tyrosine kinase inhibition via competitive binding to the ATP-binding pocket of the mutated EGFR kinase domain, preventing autophosphorylation and downstream signaling (PMID: 29401113).