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The importance of being CAFs (in cancer resistance to targeted therapies)
Sabrina Rizzolio1, Silvia Giordano1,2, Simona Corso3,4
1Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
Abstract:
In the last two decades, clinical oncology has been revolutionized by the advent of targeted drugs. However, the efficacy of these therapies is significantly limited by primary and acquired resistance, that relies not only on cell-autonomous mechanisms but also on tumor microenvironment cues. Cancer-associated fibroblasts (CAFs) are extremely plastic cells of the tumor microenvironment. They not only produce extracellular matrix components that build up the structure of tumor stroma, but they also release growth factors, chemokines, exosomes, and metabolites that affect all tumor properties, including response to drug treatment. The contribution of CAFs to tumor progression has been deeply investigated and reviewed in several works. However, their role in resistance to anticancer therapies, and in particular to molecular therapies, has been largely overlooked. This review specifically dissects the role of CAFs in driving resistance to targeted therapies and discusses novel CAF targeted therapeutic strategies to improve patient survival.
Insights
Cancer-associated fibroblasts (CAFs) drive resistance to targeted cancer therapies. Targeting CAFs offers a promising strategy to overcome drug resistance and improve patient outcomes in oncology.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Targeted drugs have revolutionized cancer treatment over the past two decades.
- Therapy efficacy is limited by primary and acquired resistance, influenced by tumor microenvironment cues.
- Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment, impacting various tumor properties.
Purpose of the Study:
- To dissect the role of CAFs in driving resistance to targeted anticancer therapies.
- To review the mechanisms by which CAFs contribute to drug resistance.
- To discuss novel therapeutic strategies targeting CAFs to improve patient survival.
Main Methods:
- Literature review focusing on the role of CAFs in targeted therapy resistance.
- Analysis of studies investigating CAF-mediated mechanisms of resistance.
- Exploration of emerging therapeutic strategies targeting CAFs.
Main Results:
- CAFs contribute significantly to both primary and acquired resistance to targeted therapies.
- CAF-secreted factors, extracellular matrix components, and metabolites influence drug response.
- The role of CAFs in resistance to molecular therapies has been historically overlooked.
Conclusions:
- CAFs are critical players in the development of resistance to targeted cancer therapies.
- Targeting CAFs presents a promising avenue for overcoming treatment resistance.
- Developing novel CAF-targeted strategies is essential for improving patient survival in oncology.
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