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

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.