Tagrisso (osimertinib)

Reference inhibitors (osimertinib-EGFR, ibrutinib-BTK, THZ1-CDK7, and THZ531-CDK12) reproduced the expected geometries and served as internal controls. Although no quantitative affinity was inferred, the consistent geometric feasibility supports their potential as structural templates for covalent-binding natural scaffolds. These results provide a qualitative, structure-based rationale for further chemoproteomic and enzymatic validation of NP-derived or hybrid compounds as potential leads in cancer therapy, expanding covalent chemical space beyond existing synthetic scaffolds.

Eugenol can effectively overcome osimertinib resistance in NSCLC by regulating glycolysis through the TRIM59/ERK signaling pathway. Eugenol could serve as a promising adjunctive therapy to improve chemotherapy efficacy and overcome drug resistance in NSCLC.

PD-L1 ≥50 % was associated with over twofold risk of progression or death in EGFR-mutant NSCLC on first-line osimertinib. Supported by meta-analysis, results suggest PD-L1 expression is a negative prognostic factor, and these patients may benefit from intensified first-line strategies with prospective evaluation.

P1/2, N=200, Active, not recruiting, Black Diamond Therapeutics, Inc. | Trial primary completion date: Jul 2025 --> Nov 2025

P1, N=8, Completed, Precision Biotech Taiwan Corp.

P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Jul 2025 --> Jul 2026

In this large real-world comparative effectiveness study using target trial emulation, first-line osimertinib was associated with substantially prolonged OS and a favorable safety profile, including lower rates of severe infections and hospitalizations, compared with first-generation EGFR-TKIs in patients with metastatic EGFR-mutant NSCLC.

The pro-tumorigenic activity of OR cells was diminished by depletion of EMT-dependent secreted proteins or the EMT-activating transcription factor ZEB1. These findings identify paracrine mechanisms by which OR cells drive LUAD progression.

A 41-year-old male with metastatic lung adenocarcinoma received gefitinib as the first-line treatment. Drug binding dynamics simulation indicated reduced binding activity of osimertinib to L747_T751del and K754E mutation sites as compared to other third- or second-generation EGFR-targeted inhibitors. This study provides the first comprehensive investigation of the L747_T751del and in cis K754E mutation and its interaction with EGFR-targeted inhibitors, offering valuable clinical guidance for treating uncommon EGFR exon 19 mutations.

In this study, we found that EGFR-TKI, including gefitinib and osimertinib, impaired WWP2-mediated proteasomal degradation of LAPTM4B. These compounds synergistically enhance the efficacy of EGFR-TKIs in NSCLC models in vitro and in vivo, with minimal toxicity. Integrative analyses of patient tissue samples, cellular models, an animal model, and cancer databases highlight the critical role of the LAPTM4B-ATP1A1-lysosomal acidification axis in EGFR-TKI resistance, providing a promising therapeutic avenue for overcoming resistance in EGFR-mutant NSCLC.

ICIs have become a standard component for resectable stageⅡ-Ⅲ NSCLC, while osimertinib and alectinib established new standards for EGFR- and ALK-positive tumors, respectively. Remaining challenges include optimal patient selection, integration with surgery, and biomarker development. Future directions point to personalized strategies incorporating circulating tumor deoxyribonucleic acid (ctDNA) monitoring and novel therapies to further enhance prognosis in resectable NSCLC.

erlotinib-, gefitinib-, and osimertinib-resistant HCC827 cell lines were established by exposing them to increasing EGFR-TKIs concentrations. A nomogram (C-index = 0.7) integrated RiskScore with clinical factors for personalized prognosis. This model bridges in vitro resistance mechanisms with clinical immune landscapes, offering a tool to stratify patients for EGFR-TKIs, immunotherapies, or combinatorial strategies.