Context can change everything. Driving 65 miles per hour on the highway is perfectly fine, but the same speed in a neighborhood could be deadly. The same is true in biology. Processes that are necessary in one context can be harmful in another.
Dr. Robert Wechsler-Reya, who directs the Tumor Development Program in Sanford-Burnham’s Cancer Center, has spent many years studying how “good” processes can also cause disease. He is particularly interested in how mechanisms that are normal in embryonic development can cause cancer when turned on in children and adults.
“We work on the relationship between development and cancer, particularly in the brain,” says Dr. Wechsler-Reya. “We’re interested in how normal stem cells and progenitor cells make decisions like when to divide, when to differentiate and what to differentiate into. We’re interested in how those decisions go wrong in cancer.”
A few years ago, Dr. Wechsler-Reya identified a new stem cell that, when functioning normally, can give rise to many different cell types in the cerebellum. But if this cell acquires certain mutations, it can also give rise to cancer. Understanding how normal proliferation and differentiation get derailed is critical to targeting cancer. Especially in the case of medulloblastoma, the most common malignant brain cancer in children. While medulloblastomas are often treatable with surgery, radiation and chemotherapy, these treatments also reduce cognitive function, social interaction and overall quality of life.
“The goal is to understand what is driving the growth of the tumor and disrupt that in a much more specific way than radiation,” says Dr. Wechsler-Reya.
While the majority of medulloblastoma patients respond to therapy, a subset resist treatment and end up dying from their disease. These patients often have mutations in the myc oncogene (a gene known to cause cancer) and, as a result, their cancer is much more aggressive, and much more likely to recur and metastasize, than other subtypes of medulloblastoma.
“We can diagnose these patients, but we really have nothing to offer them,” says Dr. Wechsler-Reya. “Ultimately, they don’t respond to current therapies. We need to find new treatment options.”
Dr. Wechsler-Reya, Dr. Yanxin Pei and colleagues have taken a number of steps in that direction–including developing a new animal model for the disease—a crucial step towards finding a treatment. They are working with researchers in Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics to find small molecule compounds that control myc and the cancer it helps generate.
Dr. Wechsler-Reya acknowledges there will be no magic pill that cures all patients. “Cancer cells adapt. They find a different way to grow. So we need to block multiple pathways. We need to develop a cocktail, like we would use to treat HIV or malaria.”