Cancer stem cells （CSC） are a rare cell population withina tumor characterized by the ability to form tumorsfollowing injection into an immunocompromised host.While the role of CSC has been clearly established inani...Cancer stem cells （CSC） are a rare cell population withina tumor characterized by the ability to form tumorsfollowing injection into an immunocompromised host.While the role of CSC has been clearly established inanimal models, evidence of their clinical relevance hasbeen harder to demonstrate. A number of markers,or combination thereof, have been used to detect andmeasure, although non-specifically, CSC in almost allhuman tumors. Several pathways have been identifiedas crucial for, but not necessarily unique to, CSC surviva 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.展开更多
文摘Cancer stem cells （CSC） are a rare cell population withina tumor characterized by the ability to form tumorsfollowing injection into an immunocompromised host.While the role of CSC has been clearly established inanimal models, evidence of their clinical relevance hasbeen harder to demonstrate. A number of markers,or combination thereof, have been used to detect andmeasure, although non-specifically, CSC in almost allhuman tumors. Several pathways have been identifiedas crucial for, but not necessarily unique to, CSC surviva 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.
