Glioblastoma’s “stem-like” cells laid bare

Haley Bridger, April 10th, 2014
  • An artist’s depiction of the “stem-like” cells in glioblastoma that may
    possess properties that give them the ability to resist treatment and
    drive cancer’s growth.
    Image by Lauren Solomon, Broad Communications

What: Glioblastoma, the most common and most aggressive form of brain cancer in adults, remains effectively incurable. Evidence suggests that “stem-like” cells help drive this difficult-to-treat disease. These cells may possess properties that give them the ability to resist treatment and drive cancer’s growth, but pinpointing them and understanding the circuitry that makes them behave the way they do has been a major challenge.

Now, through the lens of epigenomics, researchers are gaining a clearer picture of the core set of switches that can turn a cancer cell into an aggressive glioblastoma stem cell capable of driving a tumor’s growth. Instead of focusing on genetics, the research team has found that by flipping epigenetic switches that alter gene activity, they can control a tumor cell’s aggressive behavior by making it regress into a stem-cell-like state.

“The code is fairly simple,” says Mario Suvà, a Broad associated scientist and a faculty member at Massachusetts General Hospital. “It’s a difference of four transcription factors: that’s all it takes to switch from a non-aggressive brain tumor cell to a very aggressive brain tumor cell.”

In a paper appearing in Cell this week, the team describes a network of genes controlled by these four master switches, as well as insights into potential therapeutic strategies.

Why: Many of the key genetic mutations tied to glioblastoma are difficult to target with drugs. Shifting cancer cells toward a less aggressive state by flipping epigenetic switches provides a tantalizing alternative treatment method, which has been used successfully in the field of leukemia. Researchers are exploring whether similar strategies could be helpful in treating brain tumors as well.

Who: A multidisciplinary team of researchers and physicians from Massachusetts General Hospital, the Broad Institute, and the Klarman Cell Observatory led by Mario Suvà and Esther Rheinbay from the Bradley Bernstein laboratory.

Where to find it: Suvà M et al.Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells.Cell April 10, 2014. DOI: 10.1016/j.cell.2014.02.030.

For more: Watch a Broad View video about research at the intersection of epigenomics and cancer.