TGF-β Inhibitors in Metastatic Pancreatic Ductal Adenocarcinoma

Marcus A. Alvarez, Júlia Pedó Freitas, S. Mazher Hussain, Evan Glazer

Research output: Contribution to journalReview article

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC. Methods: The literature was searched for peer reviewed manuscripts regarding the use of TGF-β inhibitors in PDAC therapy and the mechanism in which TGF-β intracellular signaling effects patient survival. Results: TGF-β plays a vital, context-dependent role as both a tumor suppressor and promoter of PDAC. The downstream effects of this duality play a significant role in the immunologic response of the tumor microenvironment (TME), epithelial-mesenchymal transformation (EMT), and the development of metastatic disease. Immunologic pathways have been shown to be successful targets in the treatment of other diseases, though they have not been shown efficacious in PDAC. TGF-β-mediated EMT does play a critical role in PDAC progression in the development of metastases. The use of anti-TGF-β-based therapies in phase I and II clinical trials for metastatic PDAC demonstrate the importance of understanding the role of TGF-β in PDAC progression. Conclusion: This review clarifies the recent literature investigating the role of anti-TGF-β-based therapy in PDAC and areas ripe for targeted investigations and therapies.

Original languageEnglish (US)
JournalJournal of Gastrointestinal Cancer
DOIs
StatePublished - Jan 1 2019

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Transforming Growth Factor beta
Adenocarcinoma
Epithelial-Mesenchymal Transition
Therapeutics
Phase II Clinical Trials
Clinical Trials, Phase I
Tumor Microenvironment
Manuscripts
Mortality
Carcinogens
Neoplasm Metastasis
Survival
Incidence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology

Cite this

TGF-β Inhibitors in Metastatic Pancreatic Ductal Adenocarcinoma. / Alvarez, Marcus A.; Freitas, Júlia Pedó; Mazher Hussain, S.; Glazer, Evan.

In: Journal of Gastrointestinal Cancer, 01.01.2019.

Research output: Contribution to journalReview article

Alvarez, Marcus A. ; Freitas, Júlia Pedó ; Mazher Hussain, S. ; Glazer, Evan. / TGF-β Inhibitors in Metastatic Pancreatic Ductal Adenocarcinoma. In: Journal of Gastrointestinal Cancer. 2019.
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abstract = "Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC. Methods: The literature was searched for peer reviewed manuscripts regarding the use of TGF-β inhibitors in PDAC therapy and the mechanism in which TGF-β intracellular signaling effects patient survival. Results: TGF-β plays a vital, context-dependent role as both a tumor suppressor and promoter of PDAC. The downstream effects of this duality play a significant role in the immunologic response of the tumor microenvironment (TME), epithelial-mesenchymal transformation (EMT), and the development of metastatic disease. Immunologic pathways have been shown to be successful targets in the treatment of other diseases, though they have not been shown efficacious in PDAC. TGF-β-mediated EMT does play a critical role in PDAC progression in the development of metastases. The use of anti-TGF-β-based therapies in phase I and II clinical trials for metastatic PDAC demonstrate the importance of understanding the role of TGF-β in PDAC progression. Conclusion: This review clarifies the recent literature investigating the role of anti-TGF-β-based therapy in PDAC and areas ripe for targeted investigations and therapies.",
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