Our study demonstrated that both afatinib and osimertinib as first-line treatments offer favorable median OS in patients with advanced EGFR-mutant NSCLC. In addition, we recommend that patients receiving afatinib as first-line therapy undergo sequential osimertinib treatment, regardless of their T790M mutation status.
Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration.
Initial low-dose dacomitinib demonstrated promising efficacy with an improved safety profile in patients with EGFR exon 21-mutated NSCLC. These findings support the feasibility of a dose-optimization strategy, although further prospective studies are warranted.
Likewise, a combination of selective inhibitors of KRAS (RMC-6236/daraxonrasib), EGFR family (afatinib), and STAT3 (SD36) induced the complete regression of orthotopic PDAC tumors with no evidence of tumor resistance for over 200 d posttreatment. Of importance, this combination therapy was well tolerated. In sum, these results should guide the development of new clinical trials that may benefit PDAC patients.
Among 56 patients who received subsequent systemic therapy, clinical outcomes were comparable between ICI plus platinum doublet and platinum doublet alone. These findings indicate that afatinib and osimertinib provide comparable survival outcomes as first-line therapies for NSCLC with UMs, with treatment effects varying by molecular subtype, while subsequent ICI-based regimens may confer limited additional benefit.
This study reveals that Cd may promote the malignant progression of PC by regulating ECM remodeling through key genes such as FN1. Dacomitinib shows promise as an FN1-associated therapy, offering new insights for the precise prevention and treatment of Cd-associated PC.
12 days ago
Journal
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FN1 (Fibronectin 1) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • COL3A1 (Collagen Type III Alpha 1 Chain) • COL5A1 (Collagen Type V Alpha 1 Chain)
Detection was carried out by multiple reaction monitoring mode using the transitions m/z 634.3→184.2 for golvatinib and m/z 650.3→200.2 for golvatinib N-oxide. Further study demonstrated that CYP3A4 was the principal enzyme involved in metabolizing golvatinib. To the best of our knowledge, this is the first report combining ultra-high-performance liquid chromatography-tandem MS (UHPLC-MS/MS) with UHPLC-Quadrupole-Orbitrap-HRMS for profiling golvatinib metabolism in vitro, thereby laying a foundation for subsequent pharmacokinetic study.
12 days ago
Preclinical • Journal
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CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
Combination studies revealed that W1B acts synergistically with the EGFR inhibitor dacomitinib, effectively overcoming compensatory activation of parallel pathways...The in vivo studies on Danio rerio have shown a good safety profile, as well as strong antitumor potential of the tested compound. Therefore, these findings establish W1B as a promising derivative for the development of next-generation dual IGF1R/EGFR inhibitors in GBM.
Molecular docking simulations suggested promising drug repurposing avenues, particularly with afatinib and crizotinib, for GABRD inhibition. GABRD gene may serve as a novel biomarker in the diagnosis, prognosis and immune infiltrates of CRC patients.
Additionally, the model accurately predicted patient sensitivity to specific chemotherapeutic agents like afatinib and dasatanib...We developed a signature of lncRNAs linked to crotonylation that offers dependable prognostic insights and characterizes the immune microenvironment within GC. However, additional investigation is necessary to confirm its practical applications in clinical settings.
The patient initially received pemetrexed plus carboplatin chemotherapy. The treatment efficacy was evaluated as a partial response (PR), with manageable adverse events including skin rash and paronychia. Dacomitinib may provide sustained clinical benefit and an acceptable safety profile in lung adenocarcinoma patients with L747P mutation and bone metastases.