Peer-review started: October 1, 2014
First decision: October 28, 2014
Revised: November 26, 2014
Accepted: February 9, 2015
Article in press: February 11, 2015
Published online: March 9, 2015
Cancer stem cells (CSC) are a rare cell population within a tumor characterized by the ability to form tumors following injection into an immunocompromised host. While the role of CSC has been clearly established in animal models, evidence of their clinical relevance has been harder to demonstrate. A number of markers, or combination thereof, have been used to detect and measure, although non-specifically, CSC in almost all human tumors. Several pathways have been identified as crucial for, but not necessarily unique to, CSC survival and proliferation, and novel agents have been designed to target such pathways. A number of such agents have entered early phase development. Further, drugs that have long been marketed for non-oncological indications have been redirected to oncology as they appear to affect one or more of such pathways. This article aims to review the available evidence on the clinical relevance of CSC from a drug development standpoint and the results of early phase clinical trials of agents interfering with the above pathways. It also discusses limitations of current clinical trial design and endpoints to demonstrate anti-CSC activity as well as possible strategies to overcome these limitations.
Core tip: Cancer stem cells are a rare cell population with two embedded fundamental properties: self-renewal and differentiation into the heterogeneous lineages of cancer cells that comprise the tumor. While the identification and role of such cells has been clearly established in vitro and in animal models, uncertainty remains as to the role they play in human tumors and their relevance as therapeutic targets. The article summarizes and discusses the latest findings and challenges on cancer stem cell research, the significance of these cells beyond experimental models and suggests avenues for development of cancer stem cell targeting agents.