gefitinib

Mechanistically, galangin suppressed M2 macrophage polarization, directly interacted with the efferocytosis-related targets CAMK2A and MERTK, and reduced their expression. Together, these findings establish efferocytosis as a novel and targetable vulnerability in drug-resistant NSCLC and highlight galangin as a promising sensitizer for overcoming resistance to two major targeted therapies.

Gefitinib and osimertinib, the first-generation and third-generation EGFR-TKI, have shown promising results in patients with EGFR-mutated lung cancer in clinical treatment. Moreover, PDK1 inhibitor JX06 rendered cancer cells more sensitive to gefitinib treatment in vivo, and JX06 and gefitinib combination treatments have a synergic effect to inhibit tumor growth. In conclusion, the KDM3A/METTL16/PDK1 axis plays an important role in cancer development and TKI resistance, which may offer new prognostic biomarkers and therapeutic targets for TKI resistance in the future.

Clinically approved multikinase inhibitors-including ponatinib, gefitinib, and regorafenib-exhibit off-target RIPK2 inhibition, while selective compounds such as WEHI-345, GSK2983559, CSLP37, UH15-15, and thienopyrimidine derivatives represent key advances in selective blockade. Despite encouraging preclinical data, no RIPK2-specific inhibitor has yet achieved clinical approval due to safety and selectivity challenges. Continued structure-guided optimization, exploration of allosteric and degradation-based mechanisms, and integration into precision-medicine frameworks may ultimately enable safe and effective RIPK2-targeted therapies for inflammatory and autoimmune disorders, while the potential application in oncology remains under preclinical investigation.

Drug sensitivity analysis demonstrated that high TYMS expression positively correlated with sensitivity to Afatinib and Gefitinib, but negatively correlated with Methotrexate and Vorinostat. In conclusion, TYMS is upregulated in LUAD and may serve as an independent prognostic biomarker and therapeutic target.

The use of complex dendrimer systems allows precise modulation of membrane-targeted interactions and intracellular signaling, providing mechanistic insights into overcoming EGFREx19Del-driven resistance. Overall, these findings highlight the translational potential of integrating membrane-targeted nanotherapeutics with EGFR-directed therapies to improve outcomes in NSCLC patients.

Keyword analysis revealed a shift from molecular mechanisms to targeted therapies and immunotherapy approaches, with "chemotherapy", "gefitinib", and "mutations" emerging as the most frequent keywords. This study's bibliometric analysis of EGFR-mutant NSCLC immunotherapy reveals rapid growth but identifies key gaps: optimal immunotherapy-EGFR-tyrosine kinase inhibitors (TKIs) sequencing, predictive biomarkers, and resistance mechanisms beyond T790M linked to the tumor immune microenvironment. These insights guide future research to enhance therapeutic strategies in this evolving field.

After switching to gefitinib, the patient developed heart failure with a reduced ejection fraction, which resolved after drug withdrawal, but recurred upon rechallenge. This case represents a rare instance of severe gefitinib-induced heart failure following electrical instability associated with osimertinib and highlights the need for careful cardiac monitoring and the awareness of cumulative cardiotoxicity when switching EGFR tyrosine kinase inhibitors, even to first-generation agents which are considered to be safe.

The expression patterns of these two genes did not align with the transcriptome, with only CEACAM5 exhibiting consistent gene and protein expressions. Our findings indicate that CEACAM5 serves as a biomarker for predicting the response of patients to ER and GB treatments.

Mechanistically, ART was found to inhibit the Wnt/β-catenin pathway by upregulating GSK3β and p-β-catenin expression while downregulating β-catenin, TCF4, Cyclin D1 and c-Myc expression, thereby promoting ferroptosis. These finding revealed that ART is an effective anticancer drug that enhances the therapeutic efficacy of gefitinib in LUAD cells by inducing ferroptosis and suppressing the Wnt/β-catenin pathway, which provides a promising foundation for the combined application of ART and EGFR-TKIs in the treatment of LUAD.

Collectively, 3-formylchromone exhibits anti-tumor effect and could enhance gefitinib efficacy against lung cancer, at least partly, through inhibition of IL-6/JAK1/STAT3/cyclin D1 signaling. Thus, it can be suggested as a promising modality to investigate the potential to improve the management of lung cancer and to overcome the reduced sensitivity to gefitinib on prolonged therapy.

Patients were randomly assigned 1:1 to receive either rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo. The safety profile was consistent with previous analyses. Trial registration: NCT03866499 (ClinicalTrials.gov).

We report a 73-year-old woman with EGFR L858R-mutated NSCLC who developed LM after multiple lines of therapy, including gefitinib, osimertinib, chemotherapy, anti-angiogenic therapy, and radiotherapy. Treatment with high-dose furmonertinib (240 mg daily) combined with bevacizumab resulted in symptom relief and additional survival. Remarkably, her overall survival exceeded six years from initial diagnosis. This case highlights the potential role of dose-escalated furmonertinib as salvage therapy in LM after osimertinib resistance and underscores the importance of sequential and multimodal management in advanced EGFR-mutant NSCLC.