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Tumor stroma and its role in therapy resistance: mechanisms and therapeutic opportunities

2026/06/02 by Duy Luong, Sayed Hassan Raze Shah, Siva Sankari Sivasoorian +1 · 1 voice
Medicine · #Cancer Cells and Metastasis #Gastrointestinal Tumor Research and Treatment #Myasthenia Gravis and Thymoma

paper · doi:10.1080/17425247.2026.2651211

openalex publication_date 2026/06/02 · openalex created_date 2026/06/03 · openalex updated_date 2026/06/18

Abstract

INTRODUCTION: The tumor microenvironment (TME), composed of cancer, immune, and stromal cells together with the extracellular matrix, plays critical roles in tumor initiation, progression, metastasis, and therapeutic resistance. Although immune-targeted therapies, including immune checkpoint inhibitors and CAR-T cells, have transformed cancer treatment, stromal cells are increasingly recognized as key regulators of tumor biology. AREAS COVERED: Stromal cells regulate tumor metabolism, immune evasion, angiogenesis, and drug resistance. They originate from surrounding tissues or cellular transdifferentiation and may exert tumor-promoting or tumor-suppressive effects depending on context. Current strategies target stromal components such as hyaluronic acid and laminin for drug delivery or remodel the stroma to improve therapeutic response. Stromal-targeted delivery systems enhance penetration, specificity, safety, and biocompatibility, with promising clinical outcomes. Cancer-associated fibroblasts, mesenchymal stem cells, tumor-associated adipocytes, endothelial cells, and pericytes also represent emerging therapeutic targets. Relevant studies published through April 2025 were identified using PubMed, Scopus, and Web of Science. EXPERT OPINION: Targeting the tumor stroma represents a promising direction in oncology by improving drug delivery while advancing understanding of tumor biology and treatment resistance, supporting development of more effective, context-specific therapies.

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