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Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment.

Julia Segal1, James Cronk1, Brendan Ball1

  • 1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Cold Spring Harbor Perspectives in Medicine
|March 17, 2025
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This summary is machine-generated.

Developmental pathways shape the tumor microenvironment (TME) by recruiting immunosuppressive cells and supporting tumor growth. Understanding these pathways is crucial for targeting malignancies from their origin.

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Area of Science:

  • Oncology
  • Developmental Biology
  • Immunology

Background:

  • The tumor microenvironment (TME) comprises cellular and stromal components crucial for cancer progression.
  • The TME utilizes normal tissue development processes to facilitate tumor growth, survival, and metastasis.
  • Immunosuppressive cells and stromal support within the TME hinder antitumor immune responses.

Purpose of the Study:

  • To review the role of developmental pathways in the formation and modulation of the TME.
  • To explore how these pathways contribute to malignancy in both pediatric and adult solid tumors.

Main Methods:

  • Literature review focusing on canonical developmental signaling pathways.
  • Analysis of the involvement of Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT pathways in TME formation.
  • Examination of TME's impact on tumor progression and immune evasion.

Main Results:

  • Developmental pathways are co-opted by tumors to recruit immunosuppressive cells (e.g., macrophages, T cells).
  • Stromal cells, influenced by developmental pathways, provide trophic support, promote angiogenesis, and aid in immune suppression.
  • The TME ecosystem, shaped by developmental signaling, influences tumor behavior from inception.

Conclusions:

  • Canonical developmental pathways are key regulators of the tumor microenvironment.
  • Targeting these pathways offers potential therapeutic strategies for solid tumors.
  • Further research into developmental origins of malignancy is warranted.