Colorectal Cancer Stem Cells and Targeted Agents
Abstract
:1. Introduction
2. Colorectal Cancer Stem Cells
2.1. Origin of CR-CSCs
2.2. Identification of CR-CSCs
2.3. Cultivation of CR-CSCs
3. Agents Targeting CR-CSCs
3.1. Targeting CR-CSC Biomarkers
3.2. Targeting Signaling Pathway
3.2.1. Wnt Signaling Pathway
3.2.2. Hedgehog Signaling Pathway
3.2.3. Notch Signaling Pathway
3.2.4. PI3K/Akt/mTOR Signaling Pathway
3.2.5. JAK/STAT3 Signaling Pathway
3.3. Other Agents Targeting CR-CSCs
4. Future Prospects
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Agents | Targets of CR-CSCs | Efficacy | References |
---|---|---|---|
MCLA-158 | EFGR and Lgr5 | Effective in preclinical models | [64] |
Catumaxomab | EpCAM | Approved in the European Union for the treatment of malignant ascites | [65,66,67] |
Solidomab | EpCAM | Effective in vitro | [68,69] |
CD133-directed CAR T cells | CD133 | Effective in a phase I trial | [70] |
Cetuximab | EFGR | Effective in combination therapies | [71,72,73] |
CD133-targeted oncolyticvirus | CD133 | Effective in mice | [74] |
NCB0846 | Wnt pathway | Effective in mice | [75] |
Epigallocatechin gallate | Wnt pathway | Effective in mice | [76,77] |
XAV939 | Wnt pathway | Effective in vitro | [78] |
Phenethyl isothiocyanate and sulforaphane | Wnt pathway | Not proven effective in trials | [79,80,81] |
Salinomycin | Wnt pathway | Effective in mice | [82] |
JIB04 | Wnt pathway | Effective in mice | [83] |
CBB1003 | Wnt pathway | Effective in vitro | [84] |
YW2065 | Wnt pathway | Effective in mice | [85] |
LF3 | Wnt pathway | Effective in mice | [86] |
Dickkopf-2 | Wnt pathway | Effective in vitro | [87] |
ICG-001 | Wnt pathway | Effective in vitro | [88] |
4-Acetyl-antroquinonol B | Wnt pathway and JAK-STAT pathway | Effective in mice | [89,90] |
Diallyl trisulfide | Wnt pathway | Effective in vitro | [91] |
36-077 | Wnt pathway | Effective in vitro | [92] |
Evodiamine | Wnt and Notch pathway | Effective in vitro | [93] |
Farnesyl dimethyl chromanol | Wnt pathway | Effective in mice | [94] |
FH535 | Wnt pathway | Effective in vitro | [95] |
Agents | Targets of CR-CSCs | Efficacy | Reference |
---|---|---|---|
Vismodegib | SMO of Hedgehog pathway | Approved by FDA for the treatment of basal cell carcinoma | [110,112] |
Cyclopamine | SMO of Hedgehog pathway | Effective in vitro | [111] |
RO4929097 | γ-secretase of Notch pathway | Not proven effective in a phase II trial | [113] |
Anti-DLL4 | DLL4 of Notch pathway | Effective in a phase I trial | [114] |
Honokiol | γ-secretase of Notch pathway | Effective in mice | [115] |
Quercetin | γ-secretase of Notch pathway | Effective in mice | [116] |
α-Mangostine | Notch pathway | Effective in vitro | [117] |
BEZ235 | PI3K/Akt/mTOR pathway | Not proven effective in a phase Ib trial | [118,119] |
LY294002 | PI3K/Akt/mTOR pathway | Effective in vitro | [120] |
Piplartine | PI3K/Akt/mTOR pathway | Not proven effective in trials | [121,122] |
Rapamycin | mTOR of PI3K/Akt/mTOR pathway | Not proven effective in trials | [123,124] |
Metformin | mTOR of PI3K/Akt/mTOR pathway | Effective in combination therapies | [125] |
Atractylenolide I | PI3K/Akt/mTOR pathway | Effective in mice | [126] |
Torin-1 | PI3K/Akt/mTOR pathway | Effective in vitro | [127] |
Buparlisib | Akt of PI3K/Akt/mTOR pathway | Effective in a phase Ib trial | [128,129] |
MK-2206 | Akt of PI3K/Akt/mTOR pathway | Not proven effective in a phase II trial | [130,131] |
Curcumin and GO-Y030 | STAT3 of JAK/STAT3 signaling pathway | Effective in mice | [132] |
Napabucasin | STAT3 of JAK/STAT3 signaling pathway | Not proven effective in a phase III trial | [133] |
Agents | Targets of CR-CSCs | Efficacy | Reference |
---|---|---|---|
AM404 | FBXL5 | Effective in mice | [151] |
LY2606368 | Checkpoint kinase 1 | Effective in a phase II trial of ovarian cancer | [152,159] |
ASR352 | Checkpoint kinase 1 | Effective in vitro | [153] |
NCS30049 | Checkpoint kinase 1 | Effective in vitro | [154] |
Mefloquine | RAB5/7 | Effective in vitro | [155] |
Pitavastatin | —— | Effective in vitro | [156] |
Trichostatin A | histone deacetylase | Effective in vitro | [157] |
Dabrafenib | BRAF | Approved by FDA for the treatment of elanoma | [160] |
Mithramycin A | SP1 | Effective in vitro | [161] |
Parthenolide | USP47 | Effective in vitro | [162] |
Gambogic acid | ZFP36 | Effective in a phase IIa trial | [163,164] |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhao, H.; Han, R.; Wang, Z.; Xian, J.; Bai, X. Colorectal Cancer Stem Cells and Targeted Agents. Pharmaceutics 2023, 15, 2763. https://doi.org/10.3390/pharmaceutics15122763
Zhao H, Han R, Wang Z, Xian J, Bai X. Colorectal Cancer Stem Cells and Targeted Agents. Pharmaceutics. 2023; 15(12):2763. https://doi.org/10.3390/pharmaceutics15122763
Chicago/Turabian StyleZhao, Haobin, Ruining Han, Zhankun Wang, Junfang Xian, and Xiaosu Bai. 2023. "Colorectal Cancer Stem Cells and Targeted Agents" Pharmaceutics 15, no. 12: 2763. https://doi.org/10.3390/pharmaceutics15122763
APA StyleZhao, H., Han, R., Wang, Z., Xian, J., & Bai, X. (2023). Colorectal Cancer Stem Cells and Targeted Agents. Pharmaceutics, 15(12), 2763. https://doi.org/10.3390/pharmaceutics15122763