The Sound of Evolution
Gefitinib
Mechanism of action:
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. Gefitinib competitively binds to the ATP-binding site within the tyrosine kinase domain of the epidermal growth factor receptor, thereby preventing receptor autophosphorylation. This blocks activation of downstream PI3K/AKT, RAS/RAF/MEK/ERK, and JAK/STAT pathways, reduces survival- and proliferation-related signaling, and increases the tendency to trigger apoptotic pathways.
Reference(s):
1. Pao W et al. (2004). EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A.
2. Sordella R et al. (2004). Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science.