| 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 |
Related Documents
:
|
18953558 - Tumor-host interactions: the role of inflammation. 16452218 - An integrated computational/experimental model of tumor invasion. 19805368 - Bioinformatics construction of the human cell surfaceome. 3526938 - The evolution of clinical molecular genetics. neuroblastoma as a model tumor. 21461748 - A large pelvic mass in a 39-year-old man. 11107448 - Spontaneously occurring tumors of companion animals as models for human cancer. |
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: 2013-05-06 |
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 |
Affiliation:
|
University of Colorado Denver School of Medicine, Department of Pediatrics, Aurora, CO 80045, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 CA058187-050011/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
Previous Document: Optic neuritis associated with adalimumab in the treatment of uveitis.
Next Document: Varespladib methyl in cardiovascular disease.