Cancer Stem Cells and Response to Therapy

Abstract

The cancer stem cell (CSC) model states that cancers are organized in cellular hierarchies, which explains the functional heterogeneity often seen in tumors. Like normal tissue stem cells, CSCs are capable of self-renewal, either by symmetric or asymmetric cell division, and have the exclusive ability to reproduce malignant tumors indefinitely. Current systemic cancer therapies frequently fail to eliminate advanced tumors, which may be due to their inability to effectively target CSC populations. It has been shown that embryonic pathways such as Wnt, Hedgehog, and Notch control self-renewal and cell fate decisions of stem cells and progenitor cells. These are evolutionary conserved pathways, involved in CSC maintenance. Targeting these pathways may be effective in eradicating CSCs and preventing chemotherapy or radiotherapy resistance.

All-trans-retinoic Acid Promotes Iodine Uptake Via Up-regulating the Sodium Iodide Symporter in Medullary Thyroid Cancer Stem Cells

“…Recently, people believed that only a few cells of CSCs have the capacity to sustain the growth of tumor. And this subpopulation of cells are capable of self-renew, proliferate and differentiate into other tumor cells (Jiang et al, 2012;Tabarestani and Ghafouri-Fard, 2012;Francipane et al, 2013). It also expresses high levels of ABCG2 and OCT4, which may cause their resistance to the conventional therapies of cancer (Tabarestani and Ghafouri-Fard, 2012;Zhang et al, 2012).…”

Review on Stem Cell Therapy and their Role in Cancer Treatment

“…CSC-intrinsic mechanism can be due to more efficient DNA repair mechanisms, expression of drug pumps and altered cell cycle. CSC-extrinsic mechanisms refer to the effects of tumor microenvironment on CSCs [12]. In addition to these properties, CSCs display an anchorage-independent survival, active DNA-repair capacity and relative quiescence (slow cell cycling) [45].…”

“…Cancer stem cells prefer to reside in a hypoxic microenvironment to maintain their homeostasis rather than normal stem cells that prefer a glycolytic microenvironment. There is cross talk between CSCs and the niche, in a way that CSCs instruct the niche and are governed by the niche to proliferate, differentiate, invade and metastasize [12]. Cancer stem cells (CSCs) or tumor initiating stem-like cells (TICs) are a small subset of cancer cells which are capable of self-renewal and resist various chemotherapeutic drugs.…”

“…Understanding CSCs physiology and metabolism may be crucial for the development of novel effective therapies [12]. Tumors irrespective of their origin are heterogenous cellular entities whose growth and progression greatly depend on reciprocal interactions between genetically altered (neoplastic) cells and their non-neoplastic microenvironment [16].…”

“…Cancer stem cells reside in specialized microenvironments called niches, which have an important role in stem cell maintenance. The constituents of niche include fibroblasts, endothelial cells, perivascular cells, tissue macrophages, extracellular matrix and soluble factors excreted from cells or released from stroma [12].…”