Gefitinib

Wang L, et al. J Med Chem, 2025, 68(5), 5275-5291.

A series of dual-targeting TrxR-EGFR alkynyl-Au(I) gefitinib derivatives were synthesized by conjugating a gold(I) ligand to the 4-anilinoquinazoline scaffold of gefitinib. The derivatives were evaluated for their anticancer activity against both gefitinib-sensitive and -resistant NSCLC cell lines. L1Au2 exhibited pronounced cytotoxicity, assessed via MTT and colony formation assays, and induced apoptosis as confirmed by flow cytometry. Mechanistic studies involved in vitro inhibition assays demonstrating dual TrxR and EGFR blockade, while western blotting revealed GPX4 degradation through autophagolysosomal and proteasomal pathways. Ferroptosis induction was validated using lipid peroxidation assays, and ER stress and immunogenic cell death were monitored through markers such as CHOP and calreticulin exposure. The experimental approach highlights the application of alkynyl-Au(I) gefitinib derivatives as a novel strategy to circumvent acquired gefitinib resistance.

Ma Z, et al. Lung Cancer, 2025, 201, 108457.

In this single-arm, phase II study, gefitinib was evaluated as a neoadjuvant agent in 33 patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations. Patients received oral gefitinib (250 mg/day) for 42 days prior to surgical resection. Tumor response was assessed via objective response rate (ORR), while major pathologic response (MPR) was defined as ≤10% viable tumor. Postoperative follow-up (median 108.5 months) included disease-free survival (DFS) and overall survival (OS), and recurrence patterns were analyzed using chi-square tests. The intervention demonstrated an ORR of 54.5% and MPR of 24.2%, with MPR correlating significantly with prolonged DFS (p = 0.015) and OS (p = 0.037). Gefitinib showed superior long-term survival compared to platinum doublet chemotherapy, confirming its clinical feasibility as a neoadjuvant therapy for EGFR-mutant NSCLC.