Personalized medicine may help treat childhood brain tumors

Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.

When CIRM grantee Robert Wechsler-Reya received a Leadership Award to lure him from Duke University to the Sanford-Burnham Medical Research Institute in La Jolla, California, it was with the idea that his cancer stem cell research would point to new therapies for forms of cancer. Less than a year after moving to the state, it’s doing just that.

Wechsler-Reya and an international team of researchers have just published work describing a group of proteins that seem to drive a particularly aggressive form of the childhood brain tumor called medulloblastoma. Kids with this form of cancer have a high survival rate, but the treatment itself can leave them with a significant risk of other disorders and with mental impairments.

Wechsler-Reya’s work could help in developing drugs that effectively treat the cancer and have fewer side effects, so the kids can go on to lead a more normal life after treatment.

The work, published in the journal Cancer Cell, is dedicated to a little boy named Cameron Jackson who died earlier this year after a long battle with medulloblastoma.

Some, but not all, forms of medulloblastoma contain abnormally high levels of a gene known as Myc (pronounced “mick”). Working in mice, they discovered that these tumors are particularly dependent on a group of proteins involved in cell survival. When they exposed tumor-bearing mice to a drug that reduces the activity of those proteins, the mice lived longer.

As it happens, there are drugs that specifically target those proteins being tested in other forms of cancer. Wechsler-Reya is quoted in a press release from Sanford-Burnham:

“Obviously there are many steps between screening compounds in the lab and giving drugs to patients,” Wechsler-Reya said. “But some of the steps can be cut short if you use drugs that are already in trials or in use for other diseases.”

This work is an important step toward personalized medicine. Instead of treating all kids who have medulloblastoma with the same drug, a doctor might one day be able to screen the child’s tumor, find out which genes have gone awry, and specifically treat that tumor with the drugs that will be most effective.

You can read more on our website about CIRM grantees working toward therapies for forms of brain tumors.

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Pei, Y., Moore, C., Wang, J., Tewari, A., Eroshkin, A., Cho, Y., Witt, H., Korshunov, A., Read, T., Sun, J., Schmitt, E., Miller, C., Buckley, A., McLendon, R., Westbrook, T., Northcott, P., Taylor, M., Pfister, S., Febbo, P., & Wechsler-Reya, R. (2012). An Animal Model of MYC-Driven Medulloblastoma Cancer Cell, 21 (2), 155-167 DOI: 10.1016/j.ccr.2011.12.021