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Lazertinib: A Cardio-Safer Alternative to Osimertinib for Epidermal Growth Factor Receptor L858R/T790M Double-Mutant Tyrosine Kinase Resistant Non-Small Cell Lung Cancer.

作者信息

Gawli Chandrakant S, Nagpure Narendra R, Patil Bhatu R, Ochi Nobuaki, Takigawa Nagio, Patel Harun M

机构信息

R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.

Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.

出版信息

Drug Dev Res. 2025 Sep;86(6):e70153. doi: 10.1002/ddr.70153.

Abstract

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with "epidermal growth factor receptor (EGFR)" mutations playing a pivotal role in tumor progression and carcinogenesis. "Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)," such as Osimertinib, have significantly improved treatment outcomes by overcoming resistance mechanisms like the T790M mutation. However, Osimertinib's clinical application is limited by cardiotoxicity concerns, necessitating safer alternatives. Lazertinib, a structurally optimized third-generation EGFR-TKI, exhibits superior selectivity for mutant EGFR while sparing wild-type EGFR, thereby reducing off-target toxicities. This current opinion highlights the pharmacological properties of Lazertinib, its enhanced binding interactions, and its efficacy in overcoming resistance while demonstrating an improved safety profile. Comparative analyses reveal that Lazertinib offers stronger inhibition of key EGFR mutations, superior pharmacokinetics, and lower cardiotoxicity risks compared to Osimertinib. Additionally, Lazertinib's improved central nervous system (CNS) penetration enhances its therapeutic potential in patients with brain metastases. As ongoing clinical trials further elucidate its role, Lazertinib emerges as a promising next-generation EGFR inhibitor, offering a safer and more effective alternative for NSCLC treatment.

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