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The Cancer Stem Cell Hypothesis: Failures and Pitfalls

Rahman, Maryam MD*; Deleyrolle, Loic PhD*; Vedam-Mai, Vinata PhD*; Azari, Hassan PhD*; Abd-El-Barr, Muhammad MD, PhD*†; Reynolds, Brent A PhD*

doi: 10.1227/NEU.0b013e3181ff9eb5
Review: Editor's Choice

Based on the clonal evolution model and the assumption that the vast majority of tumor cells are able to propagate and drive tumor growth, the goal of cancer treatment has traditionally been to kill all cancerous cells. This theory has been challenged recently by the cancer stem cell (CSC) hypothesis, that a rare population of tumor cells, with stem cell characteristics, is responsible for tumor growth, resistance, and recurrence. Evidence for putative CSCs has been described in blood, breast, lung, prostate, colon, liver, pancreas, and brain. This new hypothesis would propose that indiscriminate killing of cancer cells would not be as effective as selective targeting of the cells that are driving long-term growth (ie, the CSCs) and that treatment failure is often the result of CSCs escaping traditional therapies.

The CSC hypothesis has gained a great deal of attention because of the identification of a new target that may be responsible for poor outcomes of many aggressive cancers, including malignant glioma. As attractive as this hypothesis sounds, especially when applied to tumors that respond poorly to current treatments, we will argue in this article that the proposal of a stemlike cell that initiates and drives solid tissue cancer growth and is responsible for therapeutic failure is far from proven. We will present the point of view that for most advanced solid tissue cancers such as glioblastoma multiforme, targeting a putative rare CSC population will have little effect on patient outcomes. This review will cover problems with the CSC hypothesis, including applicability of the hierarchical model, inconsistencies with xenotransplantation data, and nonspecificity of CSC markers.

*Department of Neurosurgery, University of Florida, Gainesville, Florida; †Department of Anatomical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Received, January 15, 2010.

Accepted, June 5, 2010.

Correspondence: Brent Reynolds, PhD, or Maryam Rahman, MD, Box 100265, Department of Neurosurgery, University of Florida, Gainesville, FL 32610. E-mail: or

Copyright © by the Congress of Neurological Surgeons