The cancer stem cell (CSC) hypothesis presents a fundamentally different paradigm for cancer treatment. CSCs
reflect a small fraction of tumor initiating cells capable of sustained self-renewal and differentiation to form the heterogeneous
tumor bulk. In order to cure cancer, it is necessary to eliminate cancer stem cells in addition to differentiated cancer
cells to decrease metastasis, reduce recurrence, and improve patient survival. In this article, we review cancer stem cell
signaling pathways, including Wnt, Hedgehog, and Notch, as well as interactions of CSCs with the tumor microenvironment.
We also review methods to isolate CSCs and demonstrate therapeutic efficacy of natural products to modulate these
signaling pathways for eliminating CSCs.
Keywords: Akt, cancer stem cell, hedgehog, HIF-1α, natural product, NF-κB, notch, Wnt signaling, tumor, metastasis
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