Understanding and targeting cancer stem cells: therapeutic implications and challenges

Abstract

Cancer stem cells (CSCs) have been identified as rare cell populations in many cancers, including leukemia and solid tumors. Accumulating evidence has suggested that CSCs are capable of self-renewal and differentiation into various types of cancer cells. Aberrant regulation of gene expression and some signaling pathways has been observed in CSCs compared to other tumor cells. CSCs are thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. The CSC hypothesis has recently attracted much attention due to the potential for discovery and development of CSC-related therapies and the identification of key molecules involved in controlling the unique properties of CSC populations. Over the past several years, a tremendous amount of effort has been invested in the development of new drugs, such as nanomedicines, that can take advantage of the “Achilles' heel” of CSCs by targeting cell-surface molecular markers or various signaling pathways. Novel compounds and therapeutic strategies that selectively target CSCs have been identified, some of which have been evaluated in preclinical and clinical studies. In this article, we review new findings related to the investigation of the CSC hypothesis, and discuss the crucial pathways involved in regulating the development of CSC populations and the advances in studies of drug resistance. In addition, we review new CSC-targeted therapeutic strategies aiming to eradicate malignancies.

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

“…[49][50][51] In this study, while we found that RT treatment increased the CSCs in the primary s.c. tumor compared with PBS-treated control, the percentage of ALDH high CSCs decreased significantly after RT plus CSC-DC vaccination from control (»15%) to <3%, which was also significantly less than those after treatment with RT alone (»20%) or with RT plus ALDH low DC vaccination (»12%). These results indicate that CSC-DC vaccine could induce direct targeting of CSCs.…”

Gallbladder cancer stem cell markers: An updated brief review

“…The signaling pathways utilized by both normal stem cells and CSCs overlap and are based on embryonic signaling pathways which allow self-renewal. Advancement of knowledge in the concept of Cancer Stem Cells and their encouraging results suggest new directions in the treatment of cancer as they are thought to be responsible for tumor initiation, progression, therapy resistance, relapse and metastasis [16]. The well accepted CSC markers of are CD44, CD24, CD133, CD166 and EpCAM and a few more [17] and most of them are also reported in Gall Bladder Cancer.…”

Obergurgl Research Conference Abstracts on "Cancer Stem Cells: Impact on Treatment"

“…Several landmark papers evidence dysregulation of signalling pathways in the control of self-renewal and differentiation of hepatic stem cells and include PI3K/ Akt, JAK/STAT, Wnt/β-catenin, hedgehog, Notch, NF-κB and ABC transporters to influence stemness of CSCs. [4,5] Knowledge on these pathways permits the development of molecularly targeted therapies.…”