Targeting cancer stem cell pathways for cancer therapy

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Abstract

Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.

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Author and article information

Contributors

Hongjuan Cui: hongjuan.cui@gmail.com

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 7 February 2020

Publication date PMC-release: 7 February 2020

Publication date Collection: 2020

Volume: 5

Electronic Location Identifier: 8

Affiliations

[1 ]GRID grid.263906.8, State Key Laboratory of Silkworm Genome Biology, , Southwest University, ; 400716 Chongqing, China

[2 ]GRID grid.263906.8, Cancer Center, Medical Research Institute, , Southwest University, ; 400716 Chongqing, China

[3 ]ISNI 0000 0001 1456 7807, GRID grid.254444.7, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, , Wayne State University, ; Detroit, MI 48201 USA

Article

Publisher ID: 110

DOI: 10.1038/s41392-020-0110-5

PMC ID: 7005297

PubMed ID: 32296030

SO-VID: da85e481-913f-4082-a54e-d36905d8fe77

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 5 October 2019

Date revision received : 15 December 2019

Date accepted : 19 December 2019

Funding

Funded by: the National Key Research and Development Program of China (No. 2016YFC1302204 and 2017YFC1308600), and the National Science Foundation of China (No. 81672502, 81872071, 81902664)