June 2, 2020

The Niche

Knoepfler lab stem cell blog

Know your enemy: are glioma stem cells a path to better outcomes?

GlioblastomaGlioblastoma and other related malignant glioma tumors including diffuse intrinsic pontine glioma (DIPG) are some of the most devastating of all human cancers.

You can see an image of a glioma (the white area in the brain scan) from Wikipedia above.

These brain tumors usually kill the people who get them within 1-2 years even with treatments and because today’s therapies for these cancers are themselves extremely harsh, patients’ quality of life is often very poor. Brain surgery, irradiation, and chemo can leave patients disabled. For patients with DIPG in particular, which specifically affects children, doctors have little to nothing in the way of effective treatment options for patients. It’s terrible.

We need to change that reality to provide realistic hope for these patients. The best way to do that is through a better understanding of these cancers.

A big challenge for clinically approaching these malignant glioma tumors is that the cell of origin is not clearly understood. In other words, for the question “where do malignant gliomas come from?” researchers do not so far have a whole lot of clarity. The less we understand a disease, the more difficult it is to treat it.

One intriguing, but controversial notion is that malignant glioma arise from stem cells and that these cancers contain a population of glioma stem cells (GSCs) that is clinically meaningful. For some helpful background see this fantastic review by Luis Parada’s group. Clinically targeting GSCs could lead to better outcomes for patients, but again this is a controversial area of research.

One of the talks I especially found thought provoking at the recent ISSCR 2014 meeting was Parada’s talk supporting the general notion that glioblastoma arise from stem cells. But could glioblastoma tumors also arise due to dedifferentiation of differentiated brain cells back into cancerous neural stem cells? Parada’s group found this to be very unlikely in their model system.

However, interestingly, about 18 months ago, Inder Verma’s group reported that some glioblastoma could arise from differentiated cells (a paper I covered here).

Thus, there remains an interesting debate as to both the cellular origins of these lethal tumors and the molecular mechanisms involved. Of course, different kinds of glioma could also have distinct cellular origins as well, a notion supported by some previous work as well, and that could influence the best treatment options too.

One of the goals of my own lab’s research is to better understand the potential roles of stem cells and cellular plasticity as well as the epigenome in childhood glioblastoma and DIPG as well as some other key pediatric neuronal tumors, neuroblastoma and medulloblastoma.

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