Document Detail


Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors.
MedLine Citation:
PMID:  20809868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE OF THE FIELD: Axl and/or Mer expression correlates with poor prognosis in several cancers. Until recently, the role of these receptor tyrosine kinases (RTKs) in development and progression of cancer remained unexplained. Studies demonstrating that Axl and Mer contribute to cell survival, migration, invasion, metastasis and chemosensitivity justify further investigation of Axl and Mer as novel therapeutic targets in cancer.
AREAS COVERED IN THIS REVIEW: Axl and Mer signaling pathways in cancer cells are summarized and evidence validating these RTKs as therapeutic targets in glioblastoma multiforme, NSCLC, and breast cancer is examined. A discussion of Axl and/or Mer inhibitors in development is provided.
WHAT THE READER WILL GAIN: Potential toxicities associated with Axl or Mer inhibition are addressed. We propose that the probable action of Mer and Axl inhibitors on cells within the tumor microenvironment will provide a therapeutic opportunity to target both tumor cells and the stromal components that facilitate disease progression.
TAKE HOME MESSAGE: Axl and Mer mediate multiple oncogenic phenotypes and activation of these RTKs constitutes a mechanism of chemoresistance in a variety of solid tumors. Targeted inhibition of these RTKs may be effective as anti-tumor and/or anti-metastatic therapy, particularly if combined with standard cytotoxic therapies.
Authors:
Rachel M A Linger; Amy K Keating; H Shelton Earp; Douglas K Graham
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  14     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-03-09     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  1073-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cell Movement / drug effects
Cell Survival / drug effects
Clinical Trials as Topic
Humans
Neoplasms / drug therapy*,  genetics
Oncogene Proteins / genetics,  metabolism
Protein Kinase Inhibitors / pharmacology,  therapeutic use
Proto-Oncogene Proteins / antagonists & inhibitors*,  metabolism
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*,  genetics,  metabolism
Signal Transduction / drug effects
Treatment Outcome
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
5P50CA058187/CA/NCI NIH HHS; P50 CA058187/CA/NCI NIH HHS; P50 CA058187-050011/CA/NCI NIH HHS; P50 CA058187-13/CA/NCI NIH HHS; P50 CA058187-14/CA/NCI NIH HHS; P50 CA058187-17/CA/NCI NIH HHS; R01 CA137078/CA/NCI NIH HHS; R01 CA137078-01A2/CA/NCI NIH HHS; R01 CA137078-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oncogene Proteins; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/axl receptor tyrosine kinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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