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Updated: Feb 18, 2026
A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
Remodeling of tumor stroma and response to therapy
1Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000, Australia. ganss@waimr.uwa.edu.au.
Abstract:
Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.
Insights
Solid tumors resist therapy due to their microenvironment. Modulating this tumor stroma, including blood vessels, can improve drug delivery and enhance cancer treatment efficacy.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment Research
Background:
- Solid tumors exhibit intrinsic resistance to therapies.
- The tumor microenvironment, comprising stromal cells like vasculature, inflammatory cells, and fibroblasts, supports tumor growth and immune evasion.
- Abnormal tumor vasculature leads to high interstitial fluid pressure, hindering drug penetration and promoting hypoxia, tumor growth, and metastasis.
Purpose of the Study:
- To review novel concepts for modulating the tumor stroma.
- To highlight strategies for improving therapeutic drug delivery into solid tumors.
- To discuss methods for enhancing the efficacy of cancer therapies through stroma modulation.
Main Methods:
- Review of recent scientific literature on tumor stroma modulation.
- Analysis of genetic, pharmacological, and other therapeutic approaches.
- Focus on strategies that remodel the tumor stroma for improved therapeutic access.
Main Results:
- Tumor stroma, including vasculature, can be therapeutically modulated.
- Stroma modulation enhances selective drug delivery into tumors.
- Remodeling the tumor stroma can improve the efficiency of chemotherapy and immunotherapy.
- Stroma-targeted therapies can reduce systemic toxic side effects.
Conclusions:
- Modulating the tumor microenvironment is a promising strategy to overcome therapeutic resistance in solid tumors.
- Targeting tumor stroma can improve drug penetration and enhance treatment outcomes.
- Future research should focus on developing and refining stroma-modulating therapies for increased clinical efficacy.
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