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Role of TGF-β in metastatic colon cancer: it is finally time for targeted therapy

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Abstract

Colorectal cancer (CRC) is one of the most frequent tumor types in Western countries. Approximately 20 % of patients show metastasis at the time of diagnosis, with the liver being one of the most affected organs. Transforming growth factor-beta (TGF-β) plays a regulatory role not only in the physiology of the normal colon but also in the development of CRC and its metastatic process. In this review, we analyze the molecular mechanisms leading to TGF-β dysregulation in tumor and stroma cells and the modification of the microenvironment that fosters CRC metastasis. Recent genomic studies have identified a CRC subtype with a mesenchymal and aggressive phenotype having TGF-β as a hub gene of this signature. Consistent with these findings, the inhibition of TGF-β signaling has been shown to impair experimental CRC metastasis to the liver. Based on these and other results conducted in various tumor types, the pharmaceutical industry has developed a variety of strategies to target TGF-β. We provide up-to-date information of these therapies, which are currently in preclinical or clinical trials.

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Acknowledgements

This work was supported by CIBERONC (co-funded with FEDER), RTICC (RD12/0036/0040), FIS (PI13/00093 and PI16/01352), MINECO (BIO2013-50458-EXP) and the AECC Scientific Foundation (GCB14-2170, to A.C.). Maria Villalba was supported by a FPU fellowship (FPU-14/03247).

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  1. CIBERONC, IDISNA, and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, 31008, Pamplona, Navarra, Spain

    Maria Villalba, Stephanie R. Evans & Alfonso Calvo

  2. Department of Histology and Pathology, School of Medicine, University of Navarra, 31008, Pamplona, Navarra, Spain

    Maria Villalba & Alfonso Calvo

  3. Valencia Institute of Pathology (IVP), Catholic University of Valencia School of Medicine and Odontology, Valencia, Spain

    Fernando Vidal-Vanaclocha

  4. Laboratory 2.03, Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Calle Pio XII 55, 31008, Pamplona, Spain

    Alfonso Calvo

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Correspondence to Alfonso Calvo.

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Maria Villalba and Stephanie R. Evans should be considered as first authors

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Villalba, M., Evans, S.R., Vidal-Vanaclocha, F. et al. Role of TGF-β in metastatic colon cancer: it is finally time for targeted therapy. Cell Tissue Res 370, 29–39 (2017). https://doi.org/10.1007/s00441-017-2633-9

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