Targeting TGF-β signaling in cancer

Lior H. Katz, Ying Li, Jiun Sheng Chen, Nina M. Muñoz, Avijit Majumdar, Jian Chen, Lopa Mishra*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

182 Scopus citations

Abstract

Introduction: The transforming growth factor-β (TGF-β) signaling pathway has a pivotal role in tumor suppression and yet, paradoxically, in tumor promotion. Functional context dependent insights into the TGF-β pathway are crucial in developing TGF-β-based therapeutics for cancer. Areas covered: This review discusses the molecular mechanism of the TGF-β pathway and describes the different ways of tumor suppression by TGF-β. It is then explained how tumors can evade these effects and how TGF-β contributes to further growing and spreading of some of the tumors. In the last part of the review, the data on targeting TGF-β pathway for cancer treatment is assessed. This review focuses on anti-TGF-β based treatment and other options targeting activated pathways in tumors where the TGF-β tumor suppressor pathway is lost. Pre-clinical as well up to date results of the most recent clinical trials are given. Expert opinion: Targeting the TGF-β pathway can be a promising direction in cancer treatment. However, several challenges still exist, the most important are differentiating between the carcinogenic effects of TGF-β and its other physiological roles, and delineating the tumor suppressive versus the tumor promoting roles of TGF-β in each specific tumor. Future studies are needed in order to find safer and more effective TGF-β-based drugs.

Original languageEnglish
Pages (from-to)743-760
Number of pages18
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Funding

FundersFunder number
Multidisciplinary Research Program
Science & Technology AcquisitionP30 CA016672, P30 DK56338
National Institutes of HealthRO1 CA042857, RO1 CA106614, RC2 AA019392
National Cancer InstituteP01CA130821

    Keywords

    • Cancer
    • TGF-β
    • Tumor promotion
    • Tumor suppression

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