title: Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review).
abstract: Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors (TKIs). While the pathogenic and pharmacological characteristics of common mutations in EGFR have been thoroughly investigated, those of uncommon mutations remain to be elucidated. Traditional approaches to study common mutations by randomized controlled trials are not feasible for uncommon mutations owing to their rarity. Therefore, by systematically reviewing laboratory and clinical studies of the G719X mutation, one of the uncommon mutations, we concluded that the G719X mutation was intermediately sensitive to TKIs, with an average response rate of 35.1% (47/134). Moreover, accordingly, we proposed a comprehensive model to investigate uncommon mutations in EGFR. The model involves both basic and clinical components, composed of structural analyses, functional alterations, cell viabilities and animal models with various types of clinical studies. In this review, we systematically reviewed studies of the G719X mutation and put forward a research model that could be generalized to explore uncommon mutations in diseases associated with gene mutations.
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.
authors.forename: Kaidi
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.
authors.forename: Naixin
authors.initials: N
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.
authors.forename: Shanqing
authors.initials: S
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors