TABLE 1.
Mechanisms of antitumor drug resistance mediated by CAFs.
| Tumor type | Drug resistance | Mechanisms | References |
| Breast cancer | Trastuzumab | CAFs secreting IL-6, thus activating NF-κB, JAK/STAT3 and PI3K/AKT pathways. | Mao et al., 2015 |
| Hormonal therapy | mtDNA transfer from CAFs to cancer cells via exosomes. | Sansone et al., 2017 | |
| CRC | Photodynamic therapy | CAFs reducing the sensitivity of cancer cells to photodynamic activity. | Lamberti et al., 2019 |
| Oxaliplatin | CAFs expressing lncRNA, activating Wnt/β-catenin pathway. | Deng et al., 2020 | |
| ESCC | Cisplatin | CAFs secreting IL-6, upregulating CXCR7 through STAT3/NF-κB pathway. | Qiao et al., 2018 |
| Cisplatin | CAFs secreting PAI-1 activating AKT and ERK1/2 signal. | Che et al., 2018 | |
| Gastric cancer | Cisplatin | CAFs secreting IL-8, activating NF-kB signal and increasing the expression of ABCB1. | Zhai et al., 2019 |
| Chemoresistance | CAFs expressing IL-11 and activating IL-11/IL-11R/gp130/JAK/STAT3 signal. | Ma et al., 2019 | |
| Cisplatin, paclitaxel | CAFs-derived miRNA 522 leading to ALOX15 suppression and decreased lipid-ROS accumulation. | Zhang H. et al., 2020 | |
| Lung adenocarcinoma | EGFR-TKI | CAFs expressing HGF. | Suzuki et al., 2019 |
| Cisplatin | CAFs expressing IL-11 and activating IL-11/IL-11Rα/STAT3 signal. | Tao et al., 2016 | |
| Melanoma | PLX4720 | CAFs upregulating integrin-β1, activating FAK/Src/ERK pathway. | Hirata et al., 2015 |
| NSCLC | Selumetinib, erlotinib | CAFs secreting IL-6 inducing EMT switch via JAK1/STAT3 activation. | Shien et al., 2017 |
| Crizotinib, erlotinib | CAFs utilizing lactate to increase HGF expression. | Apicella et al., 2018 | |
| Ovarian cancer | Paclitaxel | miRNA 21 derived from CAFs binding directly to its novel target APAF1. | Au Yeung et al., 2016 |
| Paclitaxel | CAF-derived HGF activating c-Met/PI3K/Akt and GRP78 signal. | Deying et al., 2017 | |
| PDAC | Gemcitabine | CAFs-derived exosomes containing Snail and microRNA-146a, inducing EMT. | Richards et al., 2017 |
| Gemcitabine | CAFs increasing the expression of HSPG2 via NF-κB signal. | Vennin et al., 2019 | |
| Gemcitabine | CAFs-derived SDF-1 promoting cancer cells SATB-1 expression. | Wei et al., 2018 | |
| Prostate cancer | Castration resistance | CAFs inducing DNA hyper- and hypo-methylation during EMT and MET. | Pistore et al., 2017 |
CRC, colorectal cancer; ESCC, esophageal squamous cell carcinoma; PAI-1, plasminogen activator inhibitor-1; CXCR7, C-X-C motif chemokine receptor 7; ABCB1, ATP-binding cassette subfamily B member 1; ALOX15, arachidonate lipoxygenase 15; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; NSCLC, non–small cell lung cancer; EMT, epithelial-to-mesenchymal transition; HGF, hepatocyte growth factor; APAF1, apoptotic protease activating factor-1; GRP78, glucose-regulated protein 78; PDAC, pancreatic ductal adenocarcinomas; HSPG2, heparin sulfate proteoglycan 2; SDF-1, stromal cell derived factor-1; SATB-1, special AT-rich sequence-binding protein 1.