Researchers identify a code of ‘molecular switches’ in Glioblastoma stem cells

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Charles S. Cobbs, MD

The Gregory Foltz, MD Endowed Director Ben & Catherine Ivy Center for Advanced Brain Tumor Treatment Swedish Neuroscience Specialists

 

A recent manuscript published in the very prestigious journal Cell, by a group of researchers at Massachusetts General Hospital, has received some attention in the brain tumor community.  http://www.massgeneral.org/about/pressrelease.aspx?id=1693 This work is quite complicated for the lay person and I will try to summarize the salient features of the paper and then described to the brain tumor patient community what, if any, the implications are for brain tumor patients in the near or distant future. To understand this paper, one needs to know that in cancers of all types, there has been a revolution in the understanding of what drives the tumors. We now believe that in addition to just the tumor cells that grow, there are a subset of cells anywhere from 1-3% or so, that are stem-like cells which have tumor initiating properties. In other words, if you took the 97% of cells out that are not stem-like cells, they would be incapable of starting a new tumor, but conversely only a few of these tumor stem-like cells could reinitiate a tumor. This is important because other researchers have shown that in the case of glioblastoma, radiation and temozolomide are likely to kill most of the non-tumor stem-like cells, but are unlikely to eradicate the stem cells, and thus you get recurrent tumor growth. This paper by the group at Massachusetts General has used elegant molecular biology and computer analysis techniques to identify four master switches at the level of DNA transcription that are responsible for keeping cells in this tumor stem-cell like state. Some of these are well-known in the cancer stem cell community such as SOX2 and OLIG2. The researchers show that these genes can essentially take a cell that has become a non cancer stem cell and divert it back to a stem cell type of fate.  In other words, if the four transcriptional regulating factors that they describe are expressed in a glioma cell, this cell will most likely revert to a stem cell type of biology. So what are the implications of this work in terms of patients in their treatment in the near term? The answer to this question is unclear. Theoretically, if one could block the activation of these four transcription factors, one could potentially divert the tumor away from a stem cell biology to more of a “differentiated tumor cell” biology. This might facilitate prevention of recurrent disease. I would caution though at this point, these findings are esoteric and have no direct implications on any treatment modality that I know of in the next five years.           Disclaimer: This is a personal blog. Any views or opinions represented in this blog are personal and belong solely to the blog author and do not represent those of people, institutions or organizations that the owner may or may not be associated with in professional or personal capacity, unless explicitly stated.  All content provided on this blog is for informational purposes only. The owner of this blog makes no representations as to the accuracy or completeness of any information on this site or found by following any link on this site. The owner will not be liable for any errors or omissions in this information nor for the availability of this information. The owner will not be liable for any losses, injuries, or damages from the display or use of this information. These terms and conditions of use are subject to change at anytime and without notice. All content provided on this blog is for informational purposes only. The owner of this blog makes no representations as to the accuracy or completeness of any information on this site or found by following any link on this site. The owner will not be liable for any errors or omissions in this information nor for the availability of this information. The owner will not be liable for any losses, injuries, or damages from the display or use of this information.

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