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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2012, Vol. 6 Issue (2) : 112-121     DOI: 10.1007/s11684-012-0199-1
Identification of cancer stem cells provides novel tumor models for drug discovery
Douglas D. Fang(), Danyi Wen, Yajun Xu
Shanghai ChemPartner Co., Ltd., 998 Halei Road, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai 201203, China
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Cancer stem cells (CSCs) have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago. Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression, drug resistance, and metastasis in both liquid and solid tumors. These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer. Since 2003, we have participated in CSC studies and encountered crucial early events in the field. This article reviews the history of CSC biology, clarifies the term and its definition, and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.

Keywords cancer stem cell      tumor model      drug discovery     
Corresponding Authors: Fang Douglas D.,   
Issue Date: 05 June 2012
URL:     OR
Fig.1  Landmark publications in the earlier years of stem cell and cancer stem cell research. The indicators and mouse strains used and the principal investigators or first authors are shown for each publication. mESCs, mouse embryonic stem cells; hESCs, human embryonic stem cells; SC, stem cell; CSC, cancer stem cell.
Stem cellsCSCs
Drug resistanceYesYes
TumorigenesisNo (except embryonic stem cells)Yes
Tab.1  Comparison of key biological properties of stem cells and CSCs
Fig.2  Identification and isolation of CSCs using cell sorting and stem cell culture technologies. Representative articles are cited.
Fig.3  CSC niche and tumor microenvironment.
Fig.4  modeling of CSC niche and tumor microenvironment by co-culturing CSCs and tumor stromal cells. A direct co-culture system may more realistically reflect a tumor microenvironment, whereas an indirect co-culture system allows for the study of not only the effects of signal proteins produced by stromal cells through a paracrine loop but also the invasive behaviors of CSCs in the presence of tumor stromal cells.
Fig.5  Use of spheroid CSC cultures for drug testing to predict antitumor activities .
Fig.6  Use of CSC-driven xenograft tumor models for efficacy studies. cultured CSCs provide a consistent cell source for the generation of xenograft tumor models. After compound treatment, xenograft tumors can be resected for analysis of CSC frequencies by flow cytometry. The self-renewal capability sustained by the remaining CSCs can be further tested by reimplantation experiments.
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