CancDer Stem Cells (CSCs) is a subset ofspite great strides being achieved in improving cancer cells with the ability to self-renew and to differentiate into non-CSC cancer cells within the tumor mass. The CSC field was shaped by great research done on hematopoietic stem cells (HSCs). HSCs are hierarchically arrangpatients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with HSCs being the founder cells that undergo asymmetric cell division giving rise to differentiated daughter cells and one quiescent stem cell with self-renewal abilitiesfatal disease. Standard cancer treatment usually involve chemotherapy and radiotherapy and these have limited effectiveness. CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. CSCs have been characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane drug transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting.

In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.