PMID- 24369725
OWN - NLM
STAT- MEDLINE
DCOM- 20140321
LR  - 20220321
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 13
DP  - 2013 Dec 27
TI  - Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean 
      patients with lung cancer.
PG  - 606
LID - 10.1186/1471-2407-13-606 [doi]
AB  - BACKGROUND: Despite an initial good response to epidermal growth factor receptor 
      (EGFR)-tyrosine kinase inhibitor (TKI), resistance to treatment eventually 
      develops. Although several resistance mechanisms have been discovered, little 
      data exist regarding Asian patient populations. METHODS: Among patients at a 
      tertiary referral hospital in Korea who initially responded well to gefitinib and 
      later acquired resistance to treatment, we selected those with enough tissues 
      obtained before EGFR-TKI treatment and after the onset of resistance to examine 
      mutations by mass spectrometric genotyping technology (Asan-Panel), MET 
      amplification by fluorescence in situ hybridization (FISH), and analysis of AXL 
      status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by 
      immunohistochemistry. RESULTS: Twenty-six patients were enrolled, all of whom 
      were diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: 10) 
      except one (squamous cell carcinoma with 19del). Secondary T790M mutation was 
      detected in 11 subjects (42.3%) and four of these patients had other co-existing 
      resistance mechanisms; increased AXL expression was observed in 5/26 patients 
      (19.2%), MET gene amplification was noted in 3/26 (11.5%), and one patient 
      acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase 
      catalytic subunit alpha isoform (PIK3CA) gene. None of the patients exhibited 
      EMT; however, increased CD56 expression suggesting neuroendocrine differentiation 
      was observed in two patients. Interestingly, conversion from L858R-mutant to 
      wild-type EGFR occurred in one patient. Seven patients (26.9%) did not exhibit 
      any known resistance mechanisms. Patients with a T790M mutation showed a more 
      favorable prognosis. CONCLUSION: The mechanisms and frequency of acquired 
      EGFR-TKI resistance in Koreans are comparable to those observed in Western 
      populations; however, more data regarding the mechanisms that drive EGFR-TKI 
      resistance are necessary.
FAU - Ji, Wonjun
AU  - Ji W
FAU - Choi, Chang-Min
AU  - Choi CM
FAU - Rho, Jin Kyung
AU  - Rho JK
FAU - Jang, Se Jin
AU  - Jang SJ
FAU - Park, Young Soo
AU  - Park YS
FAU - Chun, Sung-Min
AU  - Chun SM
FAU - Kim, Woo Sung
AU  - Kim WS
FAU - Lee, Jung-Shin
AU  - Lee JS
FAU - Kim, Sang-We
AU  - Kim SW
FAU - Lee, Dae Ho
AU  - Lee DH
FAU - Lee, Jae Cheol
AU  - Lee JC
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, 88, Olympic-ro 43-gil, Seoul, Songpa-gu, Korea. jclee@amc.seoul.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131227
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/genetics/mortality
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - DNA Mutational Analysis
MH  - Disease-Free Survival
MH  - Drug Resistance, Neoplasm
MH  - ErbB Receptors/antagonists & inhibitors/*genetics/metabolism
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Prognosis
MH  - Quinazolines/*pharmacology/therapeutic use
MH  - Republic of Korea
MH  - Retrospective Studies
MH  - Sequence Deletion
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC3877961
EDAT- 2013/12/29 06:00
MHDA- 2014/03/22 06:00
PMCR- 2013/12/27
CRDT- 2013/12/28 06:00
PHST- 2013/07/26 00:00 [received]
PHST- 2013/12/19 00:00 [accepted]
PHST- 2013/12/28 06:00 [entrez]
PHST- 2013/12/29 06:00 [pubmed]
PHST- 2014/03/22 06:00 [medline]
PHST- 2013/12/27 00:00 [pmc-release]
AID - 1471-2407-13-606 [pii]
AID - 10.1186/1471-2407-13-606 [doi]
PST - epublish
SO  - BMC Cancer. 2013 Dec 27;13:606. doi: 10.1186/1471-2407-13-606.