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TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities

Morena Fasano1, Mario Pirozzi1, Chiara Carmen Miceli1

  • 1Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy.

International Journal of Molecular Sciences
|July 13, 2024
PubMed

Insights

Transforming growth factor beta (TGF-β) signaling is key in colorectal cancer metastasis. Targeting TGF-β offers potential new therapies for metastatic colorectal cancer (mCRC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) is a global health concern, with a significant percentage of patients diagnosed with metastatic disease.
  • Transforming growth factor beta (TGF-β) signaling is integral to cellular functions, including cancer progression and metastasis.
  • Aberrant TGF-β signaling and SMAD protein mutations are prevalent in metastatic CRC (mCRC), driving tumorigenesis.

Purpose of the Study:

  • To review normal TGF-β signaling pathways.
  • To elucidate the role of TGF-β in CRC pathogenesis and metastasis.
  • To explore therapeutic strategies targeting TGF-β in mCRC.

Main Methods:

  • Literature review of TGF-β signaling in normal physiology and CRC.
  • Analysis of TGF-β's influence on epithelial-mesenchymal transition (EMT) and angiogenesis.
  • Investigation of TGF-β's impact on the tumor microenvironment (TME).

Main Results:

  • TGF-β signaling promotes neoangiogenesis through mechanisms like VEGF overexpression and pericyte differentiation.
  • TGF-β contributes to immunosuppression within the TME by affecting T cells, fibroblasts, and macrophages.
  • The pathway is implicated in epithelial-mesenchymal transition (EMT), a critical process in metastasis.

Conclusions:

  • TGF-β plays a multifaceted role in promoting CRC metastasis.
  • Targeting TGF-β signaling presents a promising therapeutic avenue for mCRC.
  • Further research into TGF-β inhibitors could lead to novel treatment options for metastatic colorectal cancer.
Keywords:
EMTTGF-βangiogenesiscolorectal cancermicroenvironment

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