Combating resistance to EGFR inhibitors

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EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors.

PURPOSE Mutant selective irreversible pyrimidine-based EGFR kinase inhibitors, including WZ4002, CO-1686, and AZD9291, are effective in preclinical models and in lung cancer patients harboring the EGFR T790M gefitinib/erlotinib resistance mutation. However, little is known about how cancers develop acquired resistance to this class of EGFR inhibitors. We sought to identify and study EGFR mutati...

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Drug Resistance to EGFR Inhibitors in Lung Cancer

Background: The discovery of mutations in epidermal growth factor receptor (EGFR) has dramatically changed the treatment of patients with non-small-cell lung cancer (NSCLC), the leading cause of cancer deaths worldwide. EGFR-targeted therapies show considerable promise, but drug resistance has become a substantial issue. Methods: We reviewed the literature to provide an overview of the drug res...

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Drug Resistance to EGFR Inhibitors in Lung Cancer

Background: The discovery of mutations in epidermal growth factor receptor (EGFR) has dramatically changed the treatment of patients with non-small-cell lung cancer (NSCLC), the leading cause of cancer deaths worldwide. EGFR-targeted therapies show considerable promise, but drug resistance has become a substantial issue. Methods: We reviewed the literature to provide an overview of the drug res...

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Mechanisms of resistance to EGFR tyrosine kinase inhibitors

Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mu...

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p53 modulates acquired resistance to EGFR inhibitors and radiation.

There is presently great interest in mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) inhibitors that are now being used widely in the treatment of a variety of common human cancers. To investigate these mechanisms, we established EGFR inhibitor-resistant clones from non-small cell lung cancer cells. A comparative analysis revealed that acquired resistance to EGFR in...

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ژورنال

عنوان ژورنال: Nature Reviews Drug Discovery

سال: 2018

ISSN: 1474-1776,1474-1784

DOI: 10.1038/nrd.2018.232