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Updated: Feb 19, 2026
A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
Why target the tumor stroma in melanoma?
James Hutchenreuther1, Andrew Leask2
1Departments of Physiology and Pharamacology and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada.
Abstract:
Melanoma metastasis is fatal. Melanoma cells are often characterized by an activated extracellular signal-regulated kinase (ERK) pathway downstream of mutations in BRAF. Therapies targeting these BRAF mutations are useful for a while; however, patients ultimately develop resistance to these therapies. Recent evidence suggests that this resistance occurs when tumor cells leave their microenvironment and migrate on a stiff, activated tumor stroma; that is, this resistance is linked to the presence of an extracellular matrix reminiscent of a fibrotic micronvironment. These data suggest that agents targeting fibrosis might be used to treat melanoma. We therefore discuss what is known about the tumor stroma in melanoma. An emergent target, CCN2 (CTGF), that is required for fibrosis, may also be a good target for drug-resistant melanoma. Intriguingly, anti-CCN2 antibodies are currently under clinical development.
Insights
Targeting fibrosis may overcome drug resistance in melanoma. Blocking CCN2 (CTGF), a key fibrosis factor, shows promise for treating advanced melanoma, with anti-CCN2 antibodies in clinical trials.
Area of Science:
- Oncology
- Cancer Biology
- Dermatology
Background:
- Melanoma metastasis is a significant cause of cancer mortality.
- BRAF mutations drive melanoma, but resistance to targeted therapies is common.
- Therapy resistance is linked to tumor cell migration within a fibrotic tumor microenvironment.
Purpose of the Study:
- To explore the role of the tumor stroma in melanoma progression and drug resistance.
- To identify potential therapeutic targets within the fibrotic tumor microenvironment.
- To evaluate CCN2 (CTGF) as a target for overcoming melanoma therapy resistance.
Main Methods:
- Review of current literature on melanoma stroma and fibrosis.
- Analysis of the role of extracellular matrix components in melanoma resistance.
- Discussion of CCN2 (CTGF) as a fibrotic mediator and potential therapeutic target.
Main Results:
- The tumor stroma, particularly fibrotic components, plays a crucial role in melanoma drug resistance.
- CCN2 (CTGF) is identified as a key mediator of fibrosis and may drive resistance.
- Anti-CCN2 antibodies are in clinical development, suggesting therapeutic potential.
Conclusions:
- Fibrosis in the tumor microenvironment is a critical factor in melanoma therapy resistance.
- Targeting CCN2 (CTGF) presents a promising strategy to overcome drug resistance in melanoma.
- Further investigation and clinical development of anti-CCN2 therapies are warranted.
