Cancer stem cells and chemoresistance: The smartest survives the raid

Abstract

Chemoresistant metastatic relapse of minimal residual disease plays a significant role for poor prognosis of cancer. Growing evidence supports a critical role of cancer stem cell (CSC) behind the mechanisms for this deadly disease. This review briefly introduces the basics of the conventional chemotherapies, updates the CSC theories, highlights the molecular and cellular mechanisms by which CSC smartly designs and utilizes multiple lines of self-defense to avoid being killed by chemotherapy, and concisely summarizes recent progress in studies on CSC-targeted therapies in the end, with the hope to help guide future research toward developing more effective therapeutic strategies to eradicate tumor cells in the patients.

Keywords: Cancer stem cell; Chemoresistance; Chemotherapy; Targeted therapy.

Figure 1

Cancer stem cell (CSCs) origins and mechanisms of formation. The three hypotheses are highlighted in bold blue arrows. 1. The epithelial to mesenchymal transition (EMT) induced by EMT-inducing factors (EIFs) turns normal epithelial cell (the red square-shaped) to fibroblast-like cell (the blue star-shaped). The latter subsequently becomes CSC particularly with mutations of oncogenes and/or tumor suppressor genes (TSGs). This process mirrors the formation of induced pluripotent cell (iPSC, green round-shaped) from normal fibroblast (red star-shaped) activated by the reprogramming factors (RPFs) shown on the left. 2. Normal adult stem cell (ASC, light-blue round shaped) is transformed into CSC by mutations of oncogene(s) and/or TSG(s). 3. EMT drives the tumor non-CSC (pink pentagon-shaped) back to be CSC.

Figure 2

The multiple lines of defense cancer stem cells use to resist chemotherapy.