PMID- 21757253
OWN - NLM
STAT- MEDLINE
DCOM- 20120627
LR  - 20211203
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 75
IP  - 1
DP  - 2012 Jan
TI  - ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for 
      ALK kinase activity.
PG  - 66-72
LID - 10.1016/j.lungcan.2011.05.027 [doi]
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion gene-positive lung cancer 
      accounts for 4-5% of non-small cell lung carcinoma. A clinical trial of the 
      specific inhibitor of ALK fusion-type tyrosine kinase is currently under way. 
      METHODS: ALK fusion gene products were analyzed immunohistochemically with the 
      materials obtained by surgery or by endobronchial ultrasound-guided 
      transbronchial needle aspiration (EBUS-TBNA). The echinoderm 
      microtubule-associated protein-like 4(EML4)-ALK or kinesin family member 5B 
      (KIF5B)-ALK translocation was confirmed by the reverse transcription polymerase 
      chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). After 
      eligibility criteria were met and informed consent was obtained, 3 patients were 
      enrolled for the Pfizer Study of Crizotinib (PF02341066), Clinical Trial 
      A8081001, conducted at Seoul National University. RESULTS: Out of 404 cases, 
      there were 14 of EML4-ALK non-small cell carcinoma (NSCLC) and one KIF5B-ALK 
      NSCLC case (8 men, 7 women; mean age, 61.9 years, range 48-82). Except for 2 
      light smokers, all patients were non-smokers. All cases were of adenocarcinoma 
      with papillary or acinar subtypes. Three were of stage IA, 5 of stage IIIA, 1 of 
      stage IIIB and 6 of stage IV. Ten patients underwent thoracotomy, 3 received 
      chemotherapy and 2 only best supportive care (BSC). One BSC and 2 chemotherapy 
      cases were enrolled for the clinical trial. Patients with advanced stages who 
      received chemotherapy or best supportive care were younger (54.0+/-6.3) than those 
      who were surgically treated (65.8+/-10.1) (p<0.05). The powerful effect of ALK 
      inhibitor on EML4-ALK NSCLC was observed. Soon after its administration, almost 
      all the multiple bone and lymph node metastases quickly disappeared. Nausea, 
      diarrhea and the persistence of a light image were the main side effects, but 
      they diminished within a few months. CONCLUSION: ALK-fusion gene was found in 
      3.7% (15/404) NSCLC cases and advanced disease with this fusion gene was 
      correlated with younger generation. The ALK inhibitor presented in this study is 
      effective in EML4-ALK NSCLC cases. A further study will be necessary to evaluate 
      the clinical effectiveness of this drug.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Kimura, Hideki
AU  - Kimura H
AD  - Division of Thoracic Diseases, Chiba Cancer Center, Chiba, Japan. 
      hkimura@chiba-cc.jp
FAU - Nakajima, Takahiro
AU  - Nakajima T
FAU - Takeuchi, Kengo
AU  - Takeuchi K
FAU - Soda, Manabu
AU  - Soda M
FAU - Mano, Hiroyuki
AU  - Mano H
FAU - Iizasa, Toshihiko
AU  - Iizasa T
FAU - Matsui, Yukiko
AU  - Matsui Y
FAU - Yoshino, Mitsuru
AU  - Yoshino M
FAU - Shingyoji, Masato
AU  - Shingyoji M
FAU - Itakura, Meiji
AU  - Itakura M
FAU - Itami, Makiko
AU  - Itami M
FAU - Ikebe, Dai
AU  - Ikebe D
FAU - Yokoi, Sana
AU  - Yokoi S
FAU - Kageyama, Hajime
AU  - Kageyama H
FAU - Ohira, Miki
AU  - Ohira M
FAU - Nakagawara, Akira
AU  - Nakagawara A
LA  - eng
PT  - Case Reports
PT  - Clinical Trial
PT  - Journal Article
DEP - 20110714
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (KIF5B protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.4.21.- (EML4 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Adenocarcinoma/drug therapy/genetics/pathology
MH  - Adenocarcinoma of Lung
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
MH  - Cell Cycle Proteins/genetics
MH  - Female
MH  - *Gene Fusion
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Kinesins/genetics
MH  - Lung Neoplasms/*drug therapy/enzymology/*genetics/pathology
MH  - Male
MH  - Microtubule-Associated Proteins/genetics
MH  - Middle Aged
MH  - Neoplasm Metastasis/drug therapy/genetics/pathology
MH  - Neoplasm Staging/methods
MH  - Oncogene Proteins, Fusion/genetics
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/*genetics
MH  - Serine Endopeptidases/genetics
EDAT- 2011/07/16 06:00
MHDA- 2012/06/28 06:00
CRDT- 2011/07/16 06:00
PHST- 2010/10/16 00:00 [received]
PHST- 2011/05/24 00:00 [revised]
PHST- 2011/05/30 00:00 [accepted]
PHST- 2011/07/16 06:00 [entrez]
PHST- 2011/07/16 06:00 [pubmed]
PHST- 2012/06/28 06:00 [medline]
AID - S0169-5002(11)00327-8 [pii]
AID - 10.1016/j.lungcan.2011.05.027 [doi]
PST - ppublish
SO  - Lung Cancer. 2012 Jan;75(1):66-72. doi: 10.1016/j.lungcan.2011.05.027. Epub 2011 
      Jul 14.