Gefitinib hydrochloride (ZD1839 hydrochloride) is a potent and orally active EGFR tyrosine kinase inhibitor (EGFR-TKI) (IC 50 = 33 nM) that selectively inhibits EGF-stimulated tumor cell growth (IC 50 = 54 nM) and that blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib hydrochloride also induces autophagy, which has antitumour activity [1] [2].

Gefitinib, at concentrations ranging from 0.01 to 0.1 mM, enhances phosphotyrosine levels, ERK signaling, and promotes proliferation and anchorage-independent growth in EGFRvIII-expressing cells, likely through EGFRvIII dimerization after prolonged exposure. Conversely, at higher concentrations (1-2 mM), gefitinib significantly reduces phosphotyrosine levels, proliferation, and anchorage-independent growth mediated by EGFRvIII. Additionally, gefitinib (ZD1839) effectively inhibits the growth of monolayers of EGF-driven, untransformed cells with an IC50 of 20 nM, and similarly impedes CALU-3 and GLC82 cell proliferation, with an IC50 of 2 μM.

Gefitinib (150 mg/kg, p.o.), when used in combination with Metformin, significantly reduces tumor growth in nude mice implanted with H1299 or CALU-3 GEF-R cells subcutaneously as tumor xenografts [3]. Conversely, in irradiated rats, Gefitinib exacerbates lung inflammation by increasing inflammatory cell infiltration and pro-inflammatory cytokine expression, yet it mitigates fibrotic lung remodeling by inhibiting lung fibroblast proliferation [4].