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Updated: Feb 16, 2026

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
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The Bone Microenvironment and Therapeutic Resistance in Spinal Metastases: Mechanisms and Clinical Implications

Laura Mittelman1, Luis O Vargas2, Matthew Abikenari3

  • 1Northwell, New Hyde Park, NY, USA.

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
|February 14, 2026
PubMed
Abstract

Insights

Spinal metastases create a treatment sanctuary in the bone niche, fostering tumor dormancy and resistance. Understanding this unique microenvironment is key to developing targeted therapies for better patient outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Microenvironment Research

Background:

  • Spinal metastases are a distinct cancer manifestation, often progressing despite systemic treatment.
  • The vertebral bone niche features hypoxia, immune suppression, and stromal signaling, creating a sanctuary for tumor dormancy and evolution.
  • These factors contribute to therapeutic resistance in spinal metastases.

Purpose of the Study:

  • To synthesize knowledge on the bone niche in spinal metastases.
  • To explain how microenvironmental and tumor-intrinsic factors drive therapeutic resistance.
  • To provide translational implications for prognosis and treatment design.

Main Methods:

  • A narrative review of English-language studies from 1990-2024.
  • Searched PubMed and Scopus for studies on pathophysiology, bone-tumor crosstalk, dormancy, immune evasion, and resistance genetics.
  • Prioritized bone-specific outcomes like skeletal progression and skeletal-related events.

Main Results:

  • Spinal metastases involve unique tumor-bone microenvironment interactions (e.g., RANK/RANKL, HIF activation).
  • Specific molecular alterations (e.g., EGFR, ALK, BRCA) and resistance mutations (e.g., T790M, BRCA reversion) emerge in bone.
  • Conventional therapies show lower efficacy in the spine, highlighting the need for site-specific strategies.

Conclusions:

  • The vertebral niche promotes treatment resistance, tumor dormancy, and evolution of resistant clones.
  • Integrating bone biology, molecular profiling, liquid biopsy, and advanced imaging is crucial for refining prognostics and treatment.
  • Reframing spinal metastases as a distinct entity is essential for developing bone-directed therapies and advancing precision oncology.
Keywords:
Bone microenvironmentImmune evasionPrecision oncologySpinal metastasesTherapeutic resistanceTumor dormancyVertebral niche

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