Abstract

Over the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. Despite these advances, tumor resistance to chemotherapy and radiation and rapid progression to metastatic disease are still seen in many patients. Evidence has shown that cancer stem cells (CSCs), a sub-population of cells that share many common characteristics with somatic stem cells (SSCs), contribute to this therapeutic failure. The most critical properties of CSCs are their self-renewal ability and their capacity for differentiation into heterogeneous populations of cancer cells. Although CSCs only constitute a low percentage of the total tumor mass, these cells can regrow the tumor mass on their own. Initially identified in leukemia, CSCs have subsequently been found in cancers of the breast, the colon, the pancreas, and the brain. Common genetic and phenotypic features found in both SSCs and CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, and TGF-β. These pathways play fundamental roles in the development as well as in the control of cell survival and cell fate and are relevant to therapeutic targeting of CSCs. The differences in the expression of membrane proteins and exosome-delivered microRNAs between SSCs and CSCs are also important to specifically target the stem cells of the cancer. Further research efforts should be directed toward elucidation of the fundamental differences between SSCs and CSCs to improve existing therapies and generate new clinically relevant cancer treatments.

Highlights

  • Over the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments

  • One of the major problems in the failure of cancer treatments is the presence of cancer stem cells (CSCs)—they are considered to be responsible for drug therapy resistance and thought to be involved in cancer initiation and metastasis

  • Cancer is described as a proliferative, invasive, and metastatic disease that is caused by an accumulation of genetic abnormalities that randomly produce a malignant cell [2]

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Summary

Introduction

The cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. The role that chronic inflammation plays in the induction of different types of CSCs is still under investigation, but cytokines secreted by tumorassociated immune cells seem to activate the necessary pathways required by cancer cells to become cancer stem cell like. The self-renewal activity of SSCs is highly regulated by different signaling pathways but this tight regulation is lost in CSCs. It has been shown that specific pathways such as Wnt/ β-catenin, Jack/Stat, TGF-β, Notch, and Sonic Hedgehog are deregulated in CSCs

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