PMID- 23325296
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20220410
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 8
IP  - 1
DP  - 2013 Mar
TI  - ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC.
PG  - 55-67
LID - 10.1007/s11523-012-0250-9 [doi]
AB  - The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a 
      subset of patients with advanced non-small cell lung cancer (NSCLC). Oncogenic 
      fusion genes, including echinoderm microtubule-associated protein-like 4 (EML4) 
      and ALK, have been detected in approximately 2-7 % of NSCLC patients. 
      Fluorescence in situ hybridization (FISH) is the recommended method for detecting 
      ALK gene rearrangement. EML4-ALK fusion genes define a molecular subset of NSCLC 
      with distinct clinical characteristic (lung adenocarcinoma, never or former 
      smoker, usually mutually exclusive with EGFR mutations). Crizotinib (PF-02341066) 
      is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the 
      receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor). 
      Crizotinib has been shown to yield important clinical benefit such as objective 
      response rate, progression-free survival (PFS), and anticipated improvements in 
      quality of life when used in pretreated patients with advanced NSCLC harboring 
      EML4-ALK gene rearrangement. Preliminary phase II data suggested that crizotinib 
      is safe and well tolerated with rapid and robust antitumor activity. A phase III 
      randomized trial in a second-line setting showed response rate and PFS (primary 
      study endpoint) advantage for crizotinib as compared to second-line chemotherapy. 
      Treatment-related adverse events, predominantly restricted to the 
      gastrointestinal and visual systems, are generally self-limiting or easily 
      managed. Crizotinib is a new standard of care for patients with advanced, 
      ALK-positive, NSCLC. In this review, we will discuss the discovery of ALK 
      rearrangements, the clinical epidemiology of lung cancer driven by ALK, the 
      clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based 
      clinical trials.
FAU - Casaluce, Francesca
AU  - Casaluce F
AD  - Department of Clinical and Experimental Medicine, Second University of Naples, 
      Naples, Italy.
FAU - Sgambato, Assunta
AU  - Sgambato A
FAU - Maione, Paolo
AU  - Maione P
FAU - Rossi, Antonio
AU  - Rossi A
FAU - Ferrara, Carmine
AU  - Ferrara C
FAU - Napolitano, Alba
AU  - Napolitano A
FAU - Palazzolo, Giovanni
AU  - Palazzolo G
FAU - Ciardiello, Fortunato
AU  - Ciardiello F
FAU - Gridelli, Cesare
AU  - Gridelli C
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130117
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 53AH36668S (Crizotinib)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/genetics/pathology
MH  - Clinical Trials, Phase II as Topic
MH  - Crizotinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - Protein Kinase Inhibitors/administration & dosage/*therapeutic use
MH  - Pyrazoles/administration & dosage/*therapeutic use
MH  - Pyridines/administration & dosage/*therapeutic use
MH  - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors
EDAT- 2013/01/18 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/01/18 06:00
PHST- 2012/10/09 00:00 [received]
PHST- 2012/12/20 00:00 [accepted]
PHST- 2013/01/18 06:00 [entrez]
PHST- 2013/01/18 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - 10.1007/s11523-012-0250-9 [doi]
PST - ppublish
SO  - Target Oncol. 2013 Mar;8(1):55-67. doi: 10.1007/s11523-012-0250-9. Epub 2013 Jan 
      17.