Gefitinib (ZD1839) (Synonyms: ZD1839)

Gefitinib (ZD1839), is a potent EGFR-TKI (EGFR tyrosine kinase inhibitor) with IC50 of 0.033 µM, selectively inhibits EGF-stimulated tumor cell growth with IC50 of 0.054 µM and that blocks EGF-stimulated EGFR (epidermal growth factor receptor) autophosphorylation in tumor cells[1].

In vitro, the NR6wtEGFR and NR6M cell lines had low levels of PLC-γ phosphorylations but the level in the NR6M cell line was more resistant to inhibition by gefitinib (IC50 of 43 and 369 nm, respectively)[2]. A gefitinib concentration above 0.1 µm decreases the colony-forming ability of NR6W and NR6wtEGFR cells and a concentration of 1.5 µm completely abolishes the ability of these cell lines to form colonies[2]. The IC50 values of four NSCLC cells for gefitinib were 18.90 µmol/L, 16.40 µmol/L, 1.794 µmol/L and 15.99 µmol/L for A549, H1975, PC9, and PC9/GR, respectively[3]. In addition, a small concentration of gefitinib (0.62 µmol/L) significantly inhibited IL-13-induced M2-like polarization of macrophages[4].

In vivo, C57BL/6 mice were treated with 20, 40 and 80 mg/kg, once-daily for 18 days, intragastrically significantly inhibited lung metastases compared with lung tumor metastatic model mice, further indicating that the lung tissue had a reduced number of metastatic lesions and cancer cells[5]. In vivo, the growth of D341 and Daoy (medulloblastoma cell lines) xenografts treated with gefitinib at 150 mg/kg per day was inhibited by approximately 50%. Ectopically overexpressed HER2 in Daoy cells significantly increased sensitivity to gefitinib's antitumor effects in vivo (tumor volume inhibition = 78%)[6].

Wakeling AE, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. 2002 Oct 15;62(20):5749-54.

Pedersen MW, et al. Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br J Cancer. 2005 Oct 17;93(8):915-23.

Sun C, et al. FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer. Respir Res. 2020 Aug 10;21(1):210.

Tariq M, et al. Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway. Acta Pharmacol Sin. 2017 Nov;38(11):1501-1511.

Fan Q, et al. Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways. Phytomedicine. 2023 Jul 25;116:154884.

Meco D, et al. Antitumor effect in medulloblastoma cells by gefitinib: Ectopic HER2 overexpression enhances gefitinib effects in vivo. Neuro Oncol. 2009 Jun;11(3):250-9.

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