Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Normal Fibroblasts and CAFs
1.2. Hypoxia Signaling Pathways
2. Mechanisms Underlying CAF Regulation and Function in Hypoxia
2.1. ECM Remodeling
2.2. Cytokines and Immune Response
2.3. Metabolic Reprogramming
2.4. Angiogenesis
2.5. Metastasis
3. Targeting CAFs for Cancer Therapy
3.1. Targeting CAF Activation and Function
3.2. CAF Depletion
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Drugs | Mechanisms | Effects | Cancer Models | Status | References |
---|---|---|---|---|---|
Tranilast | TGF-β inhibition | Inhibits CAF-mediated fibrosis by reducing pro-inflammatory cytokines | Lymphoma, Lewis lung carcinoma, gastric cancer | Preclinical | [111,112,113] |
Pirfenidone | TGF-β inhibition | Inhibits CAF activation and proliferation | Non-small-cell lung carcinoma, pancreatic cancer | Preclinical | [114,115,116,117,118] |
Minnelide | TGF-β and HIF inhibition | Induces CAF inactivation | Pancreatic cancer | Phase I-II | [119,120,121,122] |
SD208 | TGF-β inhibition | Reduces CAF-induced chemoresistance | Colorectal cancer | Preclinical | [123] |
GANT61 | GLI inhibition | Reduces CAF-induced chemoresistance | Colorectal cancer | Preclinical | [123] |
PD98059 | ERK1/2 inhibition | Inhibits CAF signaling | Melanoma | Preclinical | [124] |
LY294002 | PI3K inhibition | Inhibits CAF signaling | Melanoma | Preclinical | [124] |
ProAgio | αvβ3 inhibition | Induces apoptosis | Pancreatic cancer | Phase I | [125,126] |
AMD3100 | CXCR4 inhibition | Inhibits CAF-mediated immune evasion | Multiple myeloma, non-Hodgkin’s lymphoma, pancreatic ductal adenocarcinoma | Approved | [127,128,129] |
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Kim, I.; Choi, S.; Yoo, S.; Lee, M.; Kim, I.-S. Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment. Cancers 2022, 14, 3321. https://doi.org/10.3390/cancers14143321
Kim I, Choi S, Yoo S, Lee M, Kim I-S. Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment. Cancers. 2022; 14(14):3321. https://doi.org/10.3390/cancers14143321
Chicago/Turabian StyleKim, Iljin, Sanga Choi, Seongkyeong Yoo, Mingyu Lee, and In-San Kim. 2022. "Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment" Cancers 14, no. 14: 3321. https://doi.org/10.3390/cancers14143321