Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics

Abstract

A frequent observation in several malignancies is the development of resistance to therapy that results in frequent tumor relapse and metastasis. Much of the tumor resistance phenotype comes from its heterogeneity that halts the ability of therapeutic agents to eliminate all cancer cells effectively. Tumor heterogeneity is, in part, controlled by cancer stem cells (CSC). CSC may be considered the reservoir of cancer cells as they exhibit properties of self-renewal and plasticity and the capability of reestablishing a heterogeneous tumor cell population. The endowed resistance mechanisms of CSC are mainly attributed to several factors including cellular quiescence, accumulation of ABC transporters, disruption of apoptosis, epigenetic reprogramming, and metabolism. There is a current need to develop new therapeutic drugs capable of targeting CSC to overcome tumor resistance. Emerging in vitro and in vivo studies strongly support the potential benefits of combination therapies capable of targeting cancer stem cell-targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This review will address the main characteristics, therapeutic implications, and perspectives of targeting CSC to improve current anticancer therapeutics.

Figure 1

Targeting cancer stem cells signaling to overcome resistance of current anticancer therapy. While the conventional chemotherapy and radiotherapy eliminate more differentiated cancer cells, specific phenotypes of CSC (i.e., multidrug resistance, epigenetic reprogramming, and tumor microenvironment protection) allow them to evade the conventional treatments and avoid the cell death. Once CSC population accumulates, after conventional therapy, they start to regrowth the tumor promoting cancer recurrence. To avoid recurrence, a more efficient therapeutic regimen purposes the administration of new drugs that directly target CSC metabolism, self-renewal, differentiation or other stem cell particularities to disrupt CSC, concomitant with conventional therapies to eliminate differentiated cells.