gefitinib

Overview

Gefitinib (Iressa) is a first-generation, reversible EGFR tyrosine kinase inhibitor (TKI) with FDA approval for first-line treatment of metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. It competes with erlotinib and was largely superseded in clinical practice by third-generation osimertinib for EGFR-mutant NSCLC.

Evidence in the corpus

  • Mutually exclusive EGFR and KRAS mutations in LUAD (n=188, P<1e-7) support independent treatment stratification: EGFR-mutant tumours (enriched in never-smokers, P=0.0046) are the primary target population for gefitinib and related EGFR TKIs. PMID:18948947
  • In a PDTO functional screen of 92 sarcoma specimens, PDTOs from patients with progressive disease at follow-up were more resistant to gefitinib (p=0.048) than those from patients with stable or responding disease, suggesting EGFR pathway dependence may be diminished in clinically aggressive sarcomas PMID:39305899.
  • EGFR/ErbB signaling was implicated by pathway analysis (PubChem + WikiPathways/KEGG) in chordoma PDTOs (SARC0046_2/3, SARC0053_a, SARC0049) and an osteosarcoma subgroup; chordomas showed preferential sensitivity to TAK-285 (an EGFR/ERBB2 dual kinase inhibitor), consistent with broader EGFR pathway dependency in this histology PMID:39305899.
  • NCI-60 CellMiner pharmacogenomics study identified EGFR-pathway genomic features associated with gefitinib sensitivity in colon cancer cell lines PMID:22802077
  • TCGA lung squamous study (178 tumors) assessed EGFR pathway context; gefitinib efficacy limited by rarity of EGFR-activating mutations in squamous histology PMID:22960745
  • Cited among ERBB-targeting agents in the list of 31 potentially actionable alterations identified by HCC/ESCC genomic profiling; ERBB family alterations (mutations and amplification) identified as candidate drug targets in HCC PMID:24735922
  • Referenced as a largely unsuccessful therapeutic target in aggressive cutaneous squamous cell carcinoma (cSCC) via EGFR inhibition; gefitinib trials in cSCC noted alongside cetuximab in the context of the absence of actionable oncogenic drivers in whole-exome sequencing of 39 aggressive cSCC cases PMID:25303977
  • Cited as the sole phase II agent trialed in metastatic cutaneous SCC (cSCC), reporting an 18% CR rate; the authors argue EGFR pathway biomarker refinement (EGFR S720F, amplification) is needed before uniform EGFR targeting in this disease PMID:25589618
  • First-generation EGFR TKI; low-cost and broadly accessible in India for young-onset NSCLC patients with EGFR mutations; review cites enrichment of EGFR exon 19 deletions (52.6% of EGFR-mutant cases) in young patients as rationale for first-line use PMID:27346245
  • Mentioned as first-generation EGFR TKI in 860-patient MSK-IMPACT LUAD cohort context; L861Q and exon 18 deletion alleles had significantly lower clinical-benefit rates with first-generation TKIs, supporting evaluation of second/third-generation agents over gefitinib for these alleles PMID:28336552.

Resistance mechanisms

  • Clinical disease progression in sarcoma patients correlates with resistance to gefitinib in PDTO assays (p=0.048), implying that rapidly progressive sarcomas may have downregulated or bypassed EGFR dependency PMID:39305899.

Cancer types (linked)

  • Sarcoma (various histologies — functional PDTO screen, progressive-disease correlation)
  • CHDM — chordoma (EGFR/ErbB pathway implicated by KEGG analysis)

Sources

  • PMID:18948947 — Ding et al. 2008, Nature. Exome-scale somatic mutation landscape of 188 LUAD tumours; mutual exclusivity of EGFR and KRAS mutations supports TKI stratification.
  • PMID:39305899 — Al Shihabi et al. 2024, Cell Stem Cell. Sarcoma PDTO functional precision-medicine screen; gefitinib resistance associated with progressive disease at follow-up.

This page was processed by crosslinker on 2026-05-14. - PMID:22802077

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:25303977

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:27346245

This page was processed by wiki-cli on 2026-05-14. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14.