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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Nerve Adaptations in the Tumor Microenvironment.

Aditi Swamy1, Karishma Ravikumar1, Merlin Pious2

  • 1Amrita School of Nanosciences & Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

Cell Biochemistry and Function
|November 28, 2025
PubMed
Summary
This summary is machine-generated.

Cancer cells actively remodel nerves, altering their function in a tumor-specific manner. This bidirectional communication within the tumor microenvironment (TME) influences cancer progression and presents new therapeutic targets.

Keywords:
cancer progressioncancer–neuron crosstalkneural remodelingperineural invasiontumor innervation

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Area of Science:

  • Oncology
  • Neuroscience
  • Cancer Biology

Background:

  • The tumor microenvironment (TME) comprises cancer cells, stromal cells, immune cells, and neural elements.
  • Tumor innervation, the growth of nerves within tumors, is increasingly recognized for its role in cancer progression.
  • The reciprocal communication between cancer cells and nerves is a critical, yet underappreciated, aspect of cancer biology.

Purpose of the Study:

  • To systematically review and consolidate emerging literature on nerve adaptations within the TME.
  • To categorize neural remodeling in cancer across structural, neurochemical, bioelectrical, and transcriptional levels.
  • To highlight the bidirectional signaling axis between cancer and nerves and its implications for cancer therapy.

Main Methods:

  • Systematic literature review of studies investigating nerve-cancer interactions.
  • Analysis of diverse cancer models and experimental systems.
  • Categorization of neural adaptations based on morphological, neurochemical, and bioelectrical changes.

Main Results:

  • Cancer cells induce tumor-type-specific structural, neurochemical, and bioelectrical changes in adjacent nerve terminals.
  • These neural adaptations resemble pathways involved in nerve regeneration.
  • The tumor secretome plays a central role in mediating nerve-cancer communication.

Conclusions:

  • A bidirectional signaling axis exists between cancer and nerves, actively shaping tumor behavior.
  • Neural remodeling in cancer is a complex, multi-level phenomenon.
  • Targeting nerve-tumor interactions offers a promising therapeutic strategy for cancer treatment.