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Aberrant Transforming Growth Factor-β Signaling in Human Pancreatic Cancer: Translational Implications

  • Chapter
Transforming Growth Factor-β in Cancer Therapy, Volume II

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The most deadly form of pancreatic cancer in humans is pancreatic ductal adenocarcinoma (PDAC), a malignancy that exhibits multiple molecular alterations, including a high frequency of K-ras, p53, p16, and Smad4 mutations. PDACs express many mitogenic growth factors and their tyrosine kinase receptors, resulting in excessive activation of mitogenic pathways. These cancers also express high levels of transforming growth factor-β (TGF-β) isoforms. This review focuses on the potential role of TGF-βs in PDAC, delineating the evidence for their paracrine growth-promoting properties that enhance tumor angiogenesis, and metastasis, and underscoring the important role of Smad7 in conferring a growth and survival advantage to pancreatic cancer cells by blocking autocrine growth-inhibitory pathways while promoting the expression of genes implicated in metastasis and apoptosis resistance.

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  1. Departments of Medicine and Pharmacology and Toxicology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Murray Korc MD

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  1. Cancer Training Branch, Office of Centers, Training and Resources, National Cancer Institute, Bethesda, MD

    Sonia B. Jakowlew PhD

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Korc, M. (2008). Aberrant Transforming Growth Factor-β Signaling in Human Pancreatic Cancer: Translational Implications. In: Jakowlew, S.B. (eds) Transforming Growth Factor-β in Cancer Therapy, Volume II. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-293-9_32

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  • DOI: https://doi.org/10.1007/978-1-59745-293-9_32

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