A new class of drugs called BET inhibitors that researchers believe could significantly improve survival rates of children and adults with medulloblastoma, may have more opportunities for testing because of what we found.

Medulloblastoma is the most common malignant brain cancer occurring in children. The tumor grows near the base of the skull and at the top of the spinal cord. Often the cancer spreads via cerebrospinal fluid down the spinal cord, resulting in a cancer that is both more difficult to treat and results in lower survival rates. This type of tumor accounts for 20 percent of all pediatric brain cancer cases and has long-term survival rates only slightly above 50 percent and sometimes worse in younger patients.

Creating a more accurate medulloblastoma model

The problem with advances in new drugs to treat medulloblastoma is simply the lack of opportunity to test the drugs on tumors with the same characteristics as those found in patients in an actual clinical setting. In short, to have a test for a drug, you first need a tumor to treat.

 Using current methods of testing, researchers generally infect preclinical models with a virus that is carrying an activated gene known as MYC that, in cancers, can lead to cell proliferation and formation of tumors. Once a tumor has occurred, drug tests are administered. The issue with this testing is that the tumors produced by this shortcut method sometimes lack some of the characteristics of the real tumors found in patients at the hospital.

The reason is that this shortcut skips over the genetic controls of the MYC gene entirely, meaning BET inhibitors can’t be effectively tested since their main function is suppressing MYC itself before tumors have a chance to grow. Roussel equated this shortcut to hot-wiring a car and says her team’s findings may be like finding the key to the car. Those findings were published in the journal Scientific Reports.

Cutting the MYC switch on

Essentially, investigators devised a way to trigger the genesis of the tumor using genome editing. Specifically, a tool known as CRISPR-Cas9, is used to edit DNA sequence by cutting apart the genetic code allowing for a reassembly. But to trigger the formation of medulloblastoma in the models, the team disabled the cutting action of the CRISPR technology by using an alternate version (dCas9) that instead homes in on the MYC gene and switches it on.

Unlike the shortcut or “hot-wire” method, this option results in the formation of a tumor that shares all the characteristics of real patient cancers, allowing the testing of BET inhibitors to produce more reliable results.