Receptor tyrosine kinase genes were sequenced in non-small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1099314DOI Listing

Publication Analysis

Top Keywords

egfr mutations
12
lung cancer
12
gefitinib therapy
8
egfr
5
gefitinib
5
lung
4
mutations lung
4
cancer correlation
4
correlation clinical
4
clinical response
4

Similar Publications

Background: Human Lung Carcinoma (LC) is among the most diagnosed cancers across the world among those non-small cell lung cancer (NSCLC) comprises about 85%. Next Generation Sequencing based detection of mutations are now well established in molecular oncology. With the advent of modern diagnostic methods, it is now well known that there are several mutations and gene rearrangements which are associated with the development of LC.

View Article and Find Full Text PDF

Glioblastoma (GBM) classification involves a combination of histological and molecular signatures including IDH1/2 mutation, TERT promoter mutation, and EGFR amplification. Non-canonical mutations such as BRAF, found in 1-2% of GBMs, activate the MEK-ERK signaling pathway. This mutation can be targeted by small molecule inhibitors, offering therapeutic potential for GBM.

View Article and Find Full Text PDF

The role of human epidermal growth factor 2 (HER2) in male breast cancer (MBC) is poorly defined. A comprehensive description of HER2 status was conducted. A total of 6,015 MBC patients from 45 studies and 135 MBC patients with sequencing data were identified.

View Article and Find Full Text PDF

Introduction: Around 85% of non-small cell lung cancers (NSCLCs) are diagnosed at an advanced stage (IIIB to IV), where therapeutic options depend on molecular analysis. However, diagnostic material for molecular testing is often represented by cytological samples which are generally scarce and span a wide range of preparation types. Thus, the primary objective is to efficiently manage materials for molecular profiling.

View Article and Find Full Text PDF

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

J Med Chem

January 2025

Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!