Research And Grants

Synthetic lethality screening with methionine restriction for treatment of DIPG

DIPG is incurable cancer that is the number one cause of cancer-related deaths in children. DIPG is hard to treat because of the surgically inaccessible location, blood-brain barrier which limits some therapies and toxicity considerations related to the young age of DIPG patients. We have focused our efforts on finding therapies that target the tumor cells specifically, show low toxicity and are most easily translated for use in the clinic. We found that DIPG patient cells are extremely sensitive to the withdrawal of methionine, which is an essential amino acid that can only be obtained through diet. This means we can restrict tumor cell access by limiting it in the diet – for patients, this can be achieved by a vegan or vegan-like diet. When we limit methionine to DIPG cells, they, but not normal cells, have worse survival. Excitingly, mice with DIPG tumors in their brainstems live longer when we restrict methionine in their diets. Here, we will extend survival further by looking for drugs we can combine with methionine restriction to make its effects even better. To do this, we will use a high throughput methodology to screen thousands of compounds, identify the best combinations and test these in cell culture and in animal models. The most promising combination will be used to move to a clinical trial for DIPG.