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Review
. 2013 Jun;34(6):732-40.
doi: 10.1038/aps.2013.27. Epub 2013 May 20.

Understanding and targeting cancer stem cells: therapeutic implications and challenges

Ke Chen  1 , Ying-hui Huang, Ji-long Chen
Affiliations
Review

Understanding and targeting cancer stem cells: therapeutic implications and challenges

Ke Chen et al. Acta Pharmacol Sin. 2013 Jun.

Abstract

Cancer stem cells (CSCs) have been identified as rare cell populations in many cancers, including leukemia and solid tumors. Accumulating evidence has suggested that CSCs are capable of self-renewal and differentiation into various types of cancer cells. Aberrant regulation of gene expression and some signaling pathways has been observed in CSCs compared to other tumor cells. CSCs are thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. The CSC hypothesis has recently attracted much attention due to the potential for discovery and development of CSC-related therapies and the identification of key molecules involved in controlling the unique properties of CSC populations. Over the past several years, a tremendous amount of effort has been invested in the development of new drugs, such as nanomedicines, that can take advantage of the "Achilles' heel" of CSCs by targeting cell-surface molecular markers or various signaling pathways. Novel compounds and therapeutic strategies that selectively target CSCs have been identified, some of which have been evaluated in preclinical and clinical studies. In this article, we review new findings related to the investigation of the CSC hypothesis, and discuss the crucial pathways involved in regulating the development of CSC populations and the advances in studies of drug resistance. In addition, we review new CSC-targeted therapeutic strategies aiming to eradicate malignancies.

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Figures

Figure 1
Figure 1
Signal pathways related with cancer stem cells. Dysregulation of signal pathway network plays an important role in retaining the stemness of CSCs. Pathways and elements involved in the control of self-renewing and differentiation of cancer stem cells as well as normal stem cells include PI3K/Akt, JAK/STAT, Wnt/β-catenin, hedgehog, Notch, NF-κB, ABC superfamily and so on. Depending on these aberrant pathways, cancer stem cells acquire its unique ability to initiate carcinoma and promote recurrence after surgery.
Figure 2
Figure 2
Therapies targeting cancer stem cells. Numerous therapies aiming at eradicating cancer stem cells have been developed during these years. Four different areas could recapitulate the current popular ideas mostly. By selectively targeting surface markers of CSCs (red area), more accurate and less side effects could be achieved. With the help of modern molecular biology techniques, more and more crucial signal elements and pathways have been unearthed (green area). By intervening aberrant pathways, specific characteristics of CSCs are suppressed and promising outcome has been reported. Molecular drugs inhibiting ABC cassette (purple area) have reached the third generation (tariquidar) and some of them are undergoing clinical trials. In addition, tumor microenvironment nursing CSCs also draws much attention (blue area). Either cutting off the growth of blood vessel or exploiting the special PH environment, has showed alluring prospects.
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