Cancer stem cells: Models, mechanisms and implications for improved treatment

Abstract

Cancer stem cell research has drawn a lot of attention recently. The importance of cancer stem cell research lies in the possibility of providing new approaches for improved understanding of cancer biology and cancer treatment. However, cancer stem cell research is still at its infancy. In this review, we will discuss the concept of cancer stem cells and the commonly used approaches for isolating or enriching cancer stem cells. We then review the common features of cancer stem cells including resistance to cancer drugs and stresses such as hypoxia and radiation. We also summarize signaling pathways which might be preferentially important for cancer stem cells. Finally, we will propose a new Yin-Yang model of cancer stem cells and discuss the possibility of developing new drugs that target cancer stem cells for improved treatment of cancer.

Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs

“…Our results also indicate that tumor cell characteristics is microenvironment-dependent and bulk cancer cells can convert to CSCs under certain conditions, which are consistent with the yin-yang model of CSCs. 11 The study of Klevebring et al suggests that there may be a dynamic conversion between breast cancer CSCs and non CSCs in vivo for similar frequencies of most somatic mutations are shared between the 2 group of cells. 37 Zhou et al's study demonstrates that dormant tumor cells in ovarian cancer exhibit CSC characteristics and cisplatin enhances these characteristics.…”

“…9,10 Some researchers have proposed a more dynamic model, i.e., the yin-yang model of CSCs, in which cancer cells consist of varying growing or replicating populations (yang) and slow growing or non-dividing populations (yin), and the 2 populations may interconvert. 11 Many studies have shown that CSCs can produce CSCs and bulk cancer cells, whereas bulk cancer cells can only produce bulk cancer cells. [12][13][14][15] These results may support the hierarchy model.…”

Stem-like tumor cells confer drug resistant properties to mantle cell lymphoma

“…Various reports have shown that some C-ICs are resistant to conventional chemotherapy and radiotherapy, indicating that these resistant cells may be responsible for relapse of the disease [17,19,20,42]. Based on our recent discovery of stem-like cells in MCL, in this study we investigated whether CD45þCD197 MCL-ICs contribute to the drug resistance properties of MCL.…”

Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

“…Several of these characteristics are believed to be important in the resistance of CSC to traditional chemotherapy and radiation. 63,73,[79][80][81][82][83][84] The ability of CSC to leverage these characteristics to better handle environmental stresses and genotoxic damage potentially explains the disconnect between therapeutic response (ie, tumor burden reduction) and overall survival in the clinic. Tumors can all but be eradicated; however, if CSC persist, tumors will inevitably recur and are likely to be more aggressive given the genotoxic insults survived.…”