gefitinib

Overview

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). By inhibiting EGFR signaling, it can suppress downstream proliferative and survival pathways that drive tumor growth in susceptible cancers. Its clinical role is most established in molecularly selected NSCLC, where EGFR dependence makes tumors more responsive to EGFR-targeted therapy.

In recent biomedical research, gefitinib has also served as a model drug for studying acquired resistance to EGFR-TKIs. Investigators have used gefitinib-resistant cell and tumor systems to examine compensatory signaling networks, including AKT/P70S6K, Wnt/β-catenin pathway activity, STING1-associated immune signaling, and ferroptosis-related regulators such as GPX4 and SLC7A11/xCT. These studies reflect the broader challenge that, although gefitinib can be effective initially, resistance frequently limits durable benefit in NSCLC.

Focus of Latest Publications

Recent publications on gefitinib have focused largely on resistance mechanisms in EGFR-mutated non-small cell lung cancer and on comparative real-world safety and efficacy. A pharmacovigilance analysis using the WHO-VigiAccess database examined post-marketing adverse drug reactions for gefitinib alongside anlotinib, afatinib, and osimertinib, collecting 10,294 gefitinib reports through April 30, 2025. The study found that, at the system organ class level, gefitinib was generally associated with skin and subcutaneous tissue disorders and gastrointestinal disorders, with additional preferred-term signals showing a mix of high-frequency and strong-signal adverse reactions that were broadly consistent with labeling but included some specific ADRs.

Several recent experimental studies investigated strategies to overcome gefitinib resistance in lung adenocarcinoma and non-small cell lung cancer. Artesunate was reported to reverse gefitinib resistance in lung adenocarcinoma by suppressing cell viability, migration, invasion, and colony formation in resistant cells, while inducing ferroptosis through increased Fe2+ accumulation, ROS formation, and MDA production, along with reduced GSH/GSSG ratio and downregulation of SLC7A11 and GPX4. This effect was linked mechanistically to inhibition of the Wnt/β-catenin pathway, including changes in GSK3β, p-β-catenin, β-catenin, TCF4, Cyclin D1, and c-MYC expression. In another study, galangin restored tumor sensitivity to gefitinib in vivo and was proposed to act through a shared, mutation-independent resistance mechanism involving dysregulated efferocytosis; it suppressed M2 macrophage polarization and directly interacted with the efferocytosis-related targets CAMK2A and MERTK.

Additional work highlighted signaling pathways implicated in gefitinib resistance. One study reported that CAMK2D isoform 15 facilitates gefitinib resistance in lung adenocarcinoma via AKT phosphorylation, underscoring the role of CAMK2-related signaling in acquired resistance to EGFR-TKIs. Another study described Yifei Sanjie pill combined with gefitinib as reducing progression of EGFR-TKI-resistant non-small cell lung cancer through the YAP/ANKRD1 axis, although the abstract provided here did not include detailed results. Together, these publications emphasize ongoing efforts to identify molecular vulnerabilities that can restore gefitinib sensitivity.

Clinical comparative data also continued to position gefitinib as a relevant first-line EGFR-TKI comparator. In the phase III REZOR study, patients with EGFR-mutated advanced non-small cell lung cancer and baseline CNS metastases were randomized to rezivertinib or gefitinib; updated CNS analyses showed longer median CNS progression-free survival with rezivertinib than with gefitinib, while gefitinib still demonstrated measurable CNS activity and no new safety findings were observed. A separate real-world retrospective study from India compared first- and third-generation EGFR-TKIs and found that osimertinib was not superior to gefitinib/erlotinib based on clinical effectiveness, although it had a better safety profile.

Key Publications

• May A real-world pharmacovigilance study of four anti-non-small cell lung cancer drugs using the WHO-VigiAccess database. (Medicine, 2026, PMID 42175505): "This study used real-world data from the World Health Organization-VigiAccess database to evaluate the post-marketing adverse drug reactions (ADRs) of these 4 drugs."
• May CAMK2D isoform 15 facilitates gefitinib resistance via AKT phosphorylation in lung adenocarcinoma. (Cancer biology & medicine, 2026, PMID 42152470): "CAMK2D isoform 15 facilitates gefitinib resistance via AKT phosphorylation in lung adenocarcinoma."
• Apr Galangin Overcomes Gefitinib and Sotorasib Resistance in Non-small Cell Lung Cancer by Inhibiting Efferocytosis. (Journal of agricultural and food chemistry, 2026, PMID 42007639): "The efficacy of gefitinib and sotorasib in EGFR- and KRAS mutant non-small cell lung cancer (NSCLC) is limited by rapid drug resistance."
• Apr Artesunate reverses gefitinib resistance in lung adenocarcinoma by inducing ferroptosis and suppressing the Wnt/β-catenin pathway. (European journal of pharmacology, 2026, PMID 41967624): "In this research, the reversal effects and potential mechanisms of ART in gefitinib-resistant LUAD were investigated both in vitro and in vivo."
• Apr Rezivertinib in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Central Nervous System Metastasis: Central Nervous System Efficacy from the Phase III REZOR Study. (Cancer communications (London, England), 2026, PMID 41924561): "...rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo."
• Jun Yifei Sanjie pill combined with gefitinib reduces the progression of EGFR-TKIs-resistant non-small cell lung cancer via YAP/ANKRD1 axis. (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026, PMID 41865688): "Yifei Sanjie pill (YFSJ), a traditional Chinese herbal remedy, has been found to enhance gefitinib's effectiveness in NSCLC."
• Feb Comparison of first and third generation EGFR-TKIs for the treatment of advanced non-small cell lung cancer: A real-world study. (Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2025, PMID 39962869): "The purpose of our research was to evaluate and compare the superiority of osimertinib over gefitinib/erlotinib in terms of clinical effectiveness and safety."