TY - JOUR
T1 - Targeting the transforming growth factor-β signalling pathway in metastatic cancer
AU - Korpal, Manav
AU - Kang, Yibin
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/5
Y1 - 2010/5
N2 - Transforming growth factor (TGF)-β signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-β, which acts to promote tumour growth, invasion and colonisation of secondary organs. In light of the pro-metastasis function, many strategies are currently being explored to antagonise the TGF-β pathway as a treatment for metastatic cancers. Strategies such as using large molecule ligand traps, reducing the translational efficiency of TGF-β ligands using antisense technology, and antagonising TGF-β receptor I/II kinase function using small molecule inhibitors are the most prominent methods being explored today. Administration of anti-TGF-β therapies alone, or in combination with immunosuppressive or cytotoxic therapies, has yielded promising results in the preclinical and clinical settings. Despite these successes, the temporal- and context-dependent roles of TGF-β signalling in cancer has made it challenging to define patient subgroups that are most likely to respond, and the therapeutic regimens that will be most effective in the clinic. Novel mouse models and diagnostic tools are being developed today to circumvent these issues, which may potentially expedite anti-TGF-β drug development and clinical application.
AB - Transforming growth factor (TGF)-β signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-β, which acts to promote tumour growth, invasion and colonisation of secondary organs. In light of the pro-metastasis function, many strategies are currently being explored to antagonise the TGF-β pathway as a treatment for metastatic cancers. Strategies such as using large molecule ligand traps, reducing the translational efficiency of TGF-β ligands using antisense technology, and antagonising TGF-β receptor I/II kinase function using small molecule inhibitors are the most prominent methods being explored today. Administration of anti-TGF-β therapies alone, or in combination with immunosuppressive or cytotoxic therapies, has yielded promising results in the preclinical and clinical settings. Despite these successes, the temporal- and context-dependent roles of TGF-β signalling in cancer has made it challenging to define patient subgroups that are most likely to respond, and the therapeutic regimens that will be most effective in the clinic. Novel mouse models and diagnostic tools are being developed today to circumvent these issues, which may potentially expedite anti-TGF-β drug development and clinical application.
KW - Cancer
KW - Metastasis
KW - Molecular therapeutics
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=77950595599&partnerID=8YFLogxK
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U2 - 10.1016/j.ejca.2010.02.040
DO - 10.1016/j.ejca.2010.02.040
M3 - Article
C2 - 20307969
AN - SCOPUS:77950595599
SN - 0959-8049
VL - 46
SP - 1232
EP - 1240
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 7
ER -