title: Acquired resistance of non-small cell lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors.
abstract: Activation of epidermal growth factor receptor (EGFR) triggers anti-apoptotic signaling, proliferation, angiogenesis, invasion, metastasis, and drug resistance, which leads to development and progression of human epithelial cancers, including non-small cell lung cancer (NSCLC). Inhibition of EGFR by tyrosine kinase inhibitors such as gefitinib and erlotinib has provided a new hope for the cure of NSCLC patients. However, acquired resistance to gefitinib and erlotinib via EGFR-mutant NSCLC has occurred through various molecular mechanisms such as T790M secondary mutation, MET amplification, hepatocyte growth factor (HGF) overexpression, PTEN downregulation, epithelial-mesenchymal transition (EMT), and other mechanisms. This review will discuss the biology of receptor tyrosine kinase inhibition and focus on the molecular mechanisms of acquired resistance to tyrosine kinase inhibitors of EGFR-mutant NSCLC.
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: fariz@juntendo.ac.jp.
authors.forename: Fariz
authors.initials: F
authors.lastname: Nurwidya
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: fumiyuki@dol.hi-ho.ne.jp.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Takahashi
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: amuraka@juntendo.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: isao-k@juntendo.ac.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: mtkatou@juntendo.ac.jp.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: tshukuya@juntendo.ac.jp.
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: tajiken@juntendo.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Tajima
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: naokoh0421@hotmail.com.
authors.forename: Naoko
authors.initials: N
authors.lastname: Shimada
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan. Electronic address: kztakaha@juntendo.ac.jp.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000970:Antineoplastic Agents; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D017228:Hepatocyte Growth Factor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D051059:PTEN Phosphohydrolase; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017228:Hepatocyte Growth Factor; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077156:Gefitinib
keywords: Acquired resistance; Epidermal growth factor receptor (EGFR); Non-small cell lung cancer (NSCLC); Tyrosine kinase inhibitors