Clinical Evidence of Glioma Stem Cell

Lausanne, Switzerland -

The concept of a cancer stem cell, or "seed cell" that replenishes and sustains the tumor mass is gaining more and more momentum in scientific and corporate circles.  An example, of course, is the Oncomed-GSK deal that is estimated to be worth approximately 1.5 billion dollars, despite Oncomed being only in preclinical phases of development.   The importance of IP surrounding cancer stem cells is that these cells have unique properties that make them difficult to identify and therefore to develop drugs against them.  While in a typical tumor mass the vast majority of cells are rapidly proliferating, cancer stem cells are generally believed to reside in a quiescent state with high expression of drug efflux proteins and possessing immune suppressive properties.

One very important question is how clinically relevant are the cancer stem cell studies that exist since many of them are either performed with mouse cancers, or with human cancers in animals.  This question was addressed by a recent paper (Murat et al. Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 2008 Jun 20;26(18):3015-24).

The investigators studied clinical cases of glioblastoma, which is a type of brain tumor with a very poor prognosis, in order to define gene expression patters associated with resistance to therapy.  80 samples of glioblastoma from patients treated with radiation and adjuvant temozolomide were assessed.  Samples from patients that had poor response to therapy contained a gene expression profile similar to that observed in self-renewing stem cells, including high levels of HOX genes and CD133 (a stem cell marker found on other cancer stem cells).  These data support the in vivo relevance of cancer stem cells or cancer stem cell-like cells that associated with poor prognosis.