The advent of cancer stem cell (CSC) hypothesis has revolutionized the cancer biology community's thinking in explaining the notorious resistance of cancer to conventional chemo- and radiotherapies. The hypothesis states that the CSCs are a subpopulation within the tumor endowed with superior resistance and with the exclusive ability to self-renew, differentiate into diverse type of progeny cancer cells, and initiate tumor. Here, we review recent literature that seek out to explain such resistance of CSCs. Signaling pathways involved in the regulation of proliferation and differentiation of stem cells (e.g. Notch, Hh, and Wnt) and efficient ABC transporter systems and DNA damage response machineries are starting to be identified as the means by which CSCs out-survive their non-CSC neighbors after conventional anti-cancer treatments. Direct links between receptor tyrosine kinase pathways and CSCs are also starting to emerge as well. Lastly, a promising relationship between epithelial-mesenchymal transition and CSCs is discussed. Though the precise resistance pathway of CSCs is not yet fully elucidated, the various mechanisms highlighted here provide promise for better fundamental understanding of CSCs and the subsequent development of a more effective CSC-targeting therapeutic in the foreseeable future.
Keywords: ABC transporters; Cancer stem cells; DNA damage response; Epithelial-mesenchymal transition; Receptor tyrosine kinase pathways; Self-renewal pathways.