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Review
. 2021 Mar 9;13(5):1172.
doi: 10.3390/cancers13051172.

Cancer-Associated Fibroblast-Induced Resistance to Chemotherapy and Radiotherapy in Gastrointestinal Cancers

In-Hye Ham  1   2 , Dagyeong Lee  1   3 , Hoon Hur  1   2   3
Affiliations
Review

Cancer-Associated Fibroblast-Induced Resistance to Chemotherapy and Radiotherapy in Gastrointestinal Cancers

In-Hye Ham et al. Cancers (Basel). .

Abstract

In the past few decades, the role of cancer-associated fibroblasts (CAFs) in resistance to therapies for gastrointestinal (GI) cancers has emerged. Clinical studies focusing on GI cancers have revealed that the high expression of CAF-related molecules within tumors is significantly correlated with unfavorable therapeutic outcomes; however, the exact mechanisms whereby CAFs enhance resistance to chemotherapy and radiotherapy in GI cancers remain unclear. The cells of origin of CAFs in GI cancers include normal resident fibroblasts, mesenchymal stem cells, endothelial cells, pericytes, and even epithelial cells. CAFs accumulated within GI cancers produce cytokines, chemokines, and growth factors involved in resistance to therapies. CAF-derived exosomes can be engaged in stroma-related resistance to treatments, and several non-coding RNAs, such as miR-92a, miR-106b, CCAL, and H19, are present in CAF-derived exosomes and transferred to GI cancer cells. The CAF-induced desmoplastic reaction interferes with drug delivery to GI cancer cells, evoking resistance to chemotherapy. However, due to the heterogeneity of CAFs in GI cancers, identifying the exact mechanism underlying CAF-induced resistance may be difficult. Recent advancements in single-cell "omics" technologies could offer clues for revealing the specific subtypes and biomarkers related to resistance.

Keywords: cancer-associated fibroblasts; chemotherapy; gastrointestinal cancer; radiotherapy; resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Gene expression patterns in pretreated gastroscopically biopsied tissues of patients who underwent preoperative chemotherapy (modified from Ham et al., 2019, Mol Cancer [15]. (A). Flow diagram presenting the study scheme for the comparison of gene expression patterns using the nCounter system between chemotherapy responders and non-responders. (B). Heatmap depicting different gene expression patterns between chemotherapy responders and non-responders. Blue-colored cells in the table to the right of the heatmap indicate stroma-related genes. (C). Nine stroma-related genes were found in non-responders.
Figure 2
Figure 2
Origins of cancer-associated fibroblasts (CAFs). Sources of CAFs in gastrointestinal cancers include resident fibroblasts, endothelial cells, epithelial cells, pericytes, and bone marrow-derived mesenchymal stem cells. CAFs: cancer-associated fibroblasts, MSC: mesenchymal stem cell.
Figure 3
Figure 3
Cancer-associated fibroblasts (CAFs) orchestrate the resistance to chemoradiotherapies in the tumor microenvironment. CAFs secrete abundant chemokines, cytokines, growth factors, exosomes, and other factors.
See this image and copyright information in PMC

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