title: EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer.
abstract: T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive non-small cell lung cancer. Resistance to AZD9291 has been described. C797S mutation was reported to be a major mechanism for resistance to T790M-targeting EGFR inhibitors. This review summarizes the latest development in identifying the C797S mutation and EAI045, the novel selective inhibitor overcoming the C797S mutant.
authors.affiliation: The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing, China.
authors.forename: Shuhang
authors.initials: S
authors.lastname: Wang
authors.affiliation: SUNY Stony Brook University, Stony Brook, NY, 11794, USA.
authors.forename: Stella T
authors.initials: ST
authors.lastname: Tsui
authors.affiliation: Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, 60208, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Liu
authors.affiliation: Henan Cancer Hospital and the affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
authors.affiliation: Henan Cancer Hospital and the affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. delong_liu@nymc.edu.
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000178:Acrylamides; D000814:Aniline Compounds; D044482:Benzeneacetamides / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D044482:Benzeneacetamides; D066246:ErbB Receptors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; C000608614:EAI045; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human