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TGFβ Signaling in the Pancreatic Tumor Microenvironment

Daniel R Principe1,2, Kaytlin E Timbers2, Luke G Atia2

  • 1Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL 60612, USA.

Cancers
|October 23, 2021
PubMed

Insights

Transforming Growth Factor β (TGFβ) inhibitors show promise for pancreatic cancer (PDAC) treatment by enhancing responses to other therapies. However, TGFβ has complex roles in PDAC progression and immune evasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) has poor outcomes due to limited treatment efficacy.
  • Transforming Growth Factor β (TGFβ) signaling pathway inhibitors are emerging as potential PDAC therapeutics.
  • TGFβ exhibits dual roles in PDAC, with both tumor-suppressive and tumor-promoting functions.

Purpose of the Study:

  • To review the multifaceted roles of TGFβ signaling in pancreatic carcinogenesis.
  • To discuss the impact of TGFβ pathway genetic inactivation on PDAC.
  • To examine the clinical development of TGFβ inhibitors for PDAC.

Main Methods:

  • Literature review of studies on TGFβ signaling in pancreatic cancer.
  • Analysis of the biological consequences of TGFβ pathway genetic alterations.
  • Evaluation of clinical trial data for TGFβ inhibitors in PDAC.

Main Results:

  • TGFβ signaling promotes PDAC progression via epithelial-to-mesenchymal transition (EMT) and fibrosis.
  • TGFβ signaling contributes to immune evasion within the pancreatic tumor microenvironment (TME).
  • TGFβ inhibitors show potential to improve responses to chemotherapy and immunotherapy.

Conclusions:

  • TGFβ signaling is a critical regulator of PDAC development and progression.
  • Targeting TGFβ may offer a novel therapeutic strategy for PDAC.
  • Further research and clinical trials are needed to optimize TGFβ inhibitor use in PDAC.
Keywords:
TGFβ signalingpancreatic cancertumor microenvironment

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