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Table 2 Strategies of targeting CAFs in HCC

From: Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

Therapeutic approach Therapeutic setting Mechanism Major effects on HCC References
Engineer CAFs miR-335 Inhibit proliferation and invasion [105]
miR-320 Target PBX3 to suppress MAPK pathway Inhibit proliferation and metastasis [106]
miR-101 Target TGF-β/ SDF1-VE-cadherin/MMP2/LAMC2 networks Suppress CAFs-promoted VM formation [57]
Target CAFs’ precursors Sibrotuzumab Inhibit HSCs activation [107]
DFOG Suppress FOXM1 expression and HGF secretion Inhibit CSC features and activation of HSCs [108]
Metformin Inactivate HSCs and abrogate hepatocarcinogenesis [109]
Curcumin Inactivate ROS/ HIF-1α/CTGF signaling Suppress HSCs-induced angiogenesis and invasion [110]
α-bromomethylene phosphonate- LPA   Block the transformation from PTFs to CAFs [45]
Target paracrine productions of CAFs IL-6 neutralizing antibody Inhibit IL-6 signaling Deplete stem cell-like properties of HCC cells [65]
LY2109761 Inhibit the synthesis and release of CTGF Reduce HCC growth and dissemination [47]
CCL2,5,7 antibodies Inhibit Hh and TGF-β pathways Inhibit tumor migration [66]
T0901317 Abrogate TGF-β-induced phenotypes through LXRα interactions Suppress HCC growth [42]
RvD1 Suppress COMP secretiom by targeting FPR2/ROS/FOXM1 signaling Impede CAFs-induced EMT and stemness features of HCC cells [30]
Target CAFs-mediated signaling and pathways Dorsomorphin Inhibit SMAD signaling Impede the activation of CAFs [51]
P38 MAPK inhibitor Block CAF-M-MDSC crosstalk Provoke antitumor immunity [111]
Rapamycin Suppress mTOR-signaling pathway Inhibit HCC cells proliferation, migration and invasion [62]
Cryptotanshinone Inactivate p-STAT3 signaling Abrogate stem cell-like properties of HCC cells [65]
  1. COMP, cartilage oligomeric matrix protein; TGF-β, transforming growth factor-β; VM, vasculogenic mimicry; IL-6, interleukin 6; mTOR, mechanistic target of rapamycin kinase; STAT3, activate signal transducer and activator of Janus kinase; CCL2/5/7/12, chemokine (C–C motif) ligand 2/5/7/12; CXCL16, chemokine (C-X-C motif) ligand 16; MDSCs, marrow-derived suppressor cells; Hh, hedgehog; FOXQ1, forkhead box Q1; CTGF, connective tissue growth factor; MAPK, mitogen-activated protein kinase; RvD1, Resolvin D1; MMP, metalloproteinases; EMT, epithelial–mesenchymal transition; VM, vasculogenic mimicry; ROS, reactive oxygen species; LPA, lysophostatidic acid; HCC, hepatocellular carcinoma; CAFs, cancer-associated fibroblasts; HSCs, hepatic stellate cells; PTFs, peritumoral tissue fibroblasts