Tackling the cancer stem cells — what challenges do they pose?

Abstract

Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have together become a major focus of current cancer research, in part because of their enhanced ability to initiate and fuel tumor growth and their intrinsic resistance to conventional therapeutics. The discovery that activation in carcinoma cells of the epithelial-to-mesenchymal transition (EMT) program can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presented a possible avenue for their therapeutic manipulation. This review addresses the more recent developments in CSC research, focusing on carcinomas that are able to undergo an EMT. We discuss the signaling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for their selective elimination or induction of their differentiation, and the role of the tumor microenvironment in sustaining them. Finally, we propose ways to exploit our current knowledge of their complex biology to design novel therapies to eliminate them.

Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1–Stat3

“…Interestingly, these mechanisms are also active in CSCs (9,10). Drug resistance allows CSCs to survive conventional and even targeted therapies and is ultimately responsible for relapse (11). Thus, CSCs have become a therapeutic target of prime interest in drug discovery (12).…”

Hes1: a key role in stemness, metastasis and multidrug resistance

“…1,2 With the efforts to investigate CSCs biology, some of the molecular components that sustain CSC properties are being uncovered. One of these is the Hes1 protein.…”

Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy

“…Another strategy could be to target the phenotype induced by S100A4 overexpression. S100A4 promotes epithelial–mesenchymal transition 3, and a mesenchymal phenotype is often less sensitive to conventional cancer drugs 26. Design of novel therapies aiming at the mesenchymal, stem‐cell‐like state might thus be beneficial also for the S100A4‐positive subpopulation of tumor cells.…”