ArticleTranslational lung cancer research2015
Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M.
Article in Translational lung cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer.Cancer discovery · 2026Article
- Article
- Upfront admixing antibodies and EGFR inhibitors preempts sequential treatments in lung cancer models.EMBO molecular medicine · 2021Article
- Rational Computational Design of Fourth-Generation EGFR Inhibitors to Combat Drug-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2020Article
- Mitigating alemtuzumab-associated autoimmunity in MS: A "whack-a-mole" B-cell depletion strategy.Neurology(R) neuroimmunology & neuroinflammation · 2020Article
- Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats.Thoracic cancer · 2020Article
- How Different Substitution Positions of F, Cl Atoms in Benzene Ring of 5-Methylpyrimidine Pyridine Derivatives Affect the Inhibition Ability of EGFRMolecules (Basel, Switzerland) · 2020Article
- Deducing the Conformational Properties of a Tyrosine Kinase Inhibitor in Solution by Optical Spectroscopy and Computational Chemistry.Frontiers in chemistry · 2020Article
- TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically RelevantMolecular cancer research : MCR · 2019Article
- Liquid chromatography-tandem mass spectrometry metabolic profiling of nazartinib reveals the formation of unexpected reactive metabolites.Royal Society open science · 2019Article
- Utilization of Archived Plasma to Detect Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer Patients.Biopreservation and biobanking · 2019Article
- Reactive intermediates in naquotinib metabolism identified by liquid chromatography-tandem mass spectrometry: phase I metabolic profiling.RSC advances · 2019Article
- Article
- Newly emergent acquired EGFR exon 18 G724S mutation after resistance of a T790M specific EGFR inhibitor osimertinib in non-small-cell lung cancer: a case report.OncoTargets and therapy · 2019Article
- Article
- [Disparities of EGFR mutations between Biopsy and Rebiopsy in Non-small Cell Lung Cancer Patients].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2018Article
- Characterization of reactive intermediates formation in dacomitinib metabolism and bioactivation pathways elucidation by LC-MS/MS:RSC advances · 2018Article
- Review
- Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance.Oncotarget · 2018Review
- An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors.EMBO molecular medicine · 2018Article
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2 authors.
Funding
Abstract
Epidermal growth factor receptor (EGFR) mutations, especially EGFR-exon 19 deletions and EGFR-L858R, are the most frequent actionable genomic events in lung adenocarcinomas. Tumors arise due to constitutively activated EGFR signaling and are susceptible to EGFR tyrosine kinase inhibitors (TKIs). First generation EGFR TKIs (gefitinib and erlotinib) and the second generation EGFR TKI afatinib are approved worldwide. Although targeted therapies against EGFR mutants induce dramatic initial responses, acquired resistance (through multiple biological mechanisms) to erlotinib, gefitinib and afatinib emerges within the first 1-2 years of continued monotherapy. EGFR-T790M accounts for more than half of acquired resistance to first or second generation EGFR TKIs by modifying ATP affinity and drug binding kinetics. Two new studies have shown that two covalent pyrimidine inhibitors-AZD9291 and rociletinib of EGFR-T790M (i.e., third generation EGFR TKIs) shown remarkable clinical activity in patients with acquired resistance to erlotinib, gefitinib and afatinib when the tumor carries EGFR-T790M in conjunction with an activating mutation. However, and regrettably, acquired resistance to these third generation EGFR TKIs has already been reported in preclinical models and clinical specimens; such as a tertiary mutation at EGFR-C797S that prevents covalent binding of EGFR TKIs. The experience with sequential EGFR TKI monotherapy highlights tumor heterogeneity and adaptability (i.e., relentless game of whack-a-mole played between TKIs and cancer), and will help shape future clinical development of novel combinatory approaches to manage EGFR mutated lung adenocarcinomas.
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