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PMID: 17906455 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Targeting transforming growth factor-beta signaling.

Current opinion in oncology ·Vol. 19 ·No. 6 ·2007-11-00 ·Pages 579-85

Pennison M, Pasche B

Abstract

Most cancers are characterized by excessive transforming growth factor-beta production by tumors, which can promote tumor growth and mediate epithelial-to-mesenchymal transition. Transforming growth factor-beta also has the ability to overproduce extracellular matrix components in response to injury and other stimuli. There are many strategies undergoing current evaluation for inhibiting the deleterious biological effects of transforming growth factor-beta by disrupting its signaling at various levels. The current review focuses on the recent advances made in this area, and the potential of these strategies in the clinical treatment of cancer and fibrosis. Four main strategies used most recently for disrupting transforming growth factor-beta signaling are brought into focus in this review: inhibition or sequestration of the transforming growth factor-beta protein ligands, inhibition of transforming growth factor-beta receptor kinase activity, inhibition of SMAD signaling downstream of transforming growth factor-beta kinase activity and restoration of antitumor immunity upon transforming growth factor-beta inhibition. Various techniques currently used to employ these four strategies are discussed. Several lines of evidence suggest that altered transforming growth factor-beta signaling contributes to tumor progression and metastasis as well as development of fibrosis. Accumulating data from preclinical and clinical studies indicate that antagonizing aberrant transforming growth factor-beta signaling is a promising novel therapeutic approach in cancer and fibrotic disorders.

MeSH Terms
Antineoplastic Agents/therapeutic use Clinical Trials as Topic Disease Progression Extracellular Matrix/metabolism Fibrosis/pathology Gene Expression Regulation, Neoplastic Humans Ligands Models, Biological Neoplasm Metastasis Neoplasms/drug therapy,pathology Signal Transduction Transforming Growth Factor beta/antagonists & inhibitors,metabolism
Chemicals
Antineoplastic Agents Ligands Transforming Growth Factor beta
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pennison Michael
Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Pasche Boris
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Article Info
Journal
Current opinion in oncology
Abbr.
Curr Opin Oncol
ISSN
1040-8746
DOI
10.1097/CCO.0b013e3282f0ad0e
Published
2007-11-00
Pages
579-85
Language
English
Region
United States
NLM ID
9007265
PMCID
PMC2640227
Subset
IM
Grants
NCI NIH HHS · CA108741 · United States
NCI NIH HHS · R01 CA108741 · United States
NCI NIH HHS · R01 CA112520-01A1 · United States
NCI NIH HHS · R01 CA112520 · United States
NCI NIH HHS · R01 CA108741-01A2 · United States
NCI NIH HHS · CA112520 · United States
NCI NIH HHS · P30 CA012197 · United States
External Links
PubMed source DOI: 10.1097/CCO.0b013e3282f0ad0e PMC Full Text View journal details
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