The African bull elephant is the largest land mammal on the planet, comprised of trillions of cells that should ostensibly be a breeding ground for cancer. But because of an evolutionary anomaly, elephants don’t get cancer, a fact that fascinates Markus Müschen, M.D., Ph.D., chair of the Department of Systems Biology and the Norman and Sadie Lee Foundation Professorship in Pediatrics.
Müschen and his team are committed to ending childhood cancer. Part of their research is an effort to find the cancer suppression genome found in elephants and apply that to the treatment of childhood cancers, particularly acute lymphoblastic leukemia (ALL).
“It has to do with how cells take care of the genome, in preparing, correcting and making sure a mutation into cancer doesn’t happen,” said Müschen of the pachyderm phenomenon. “Elephants are quite similar to humans in terms of lifespan, but of course have many, many more cells. Their cancer resistance may have something to do with the TP53 gene, which we have as well.”
A protein that can act as a tumor suppressor, TP53 is among the most studied genes in molecular biology. While each of us has two copies of TP53 from our parents, elephants have 40 copies, which genetically gives them 20 times the tumor-suppressing power. Müschen studies the genetic causes of childhood leukemia, specifically the factors that cause relapse in some but not others. He thinks that those resistant to relapse might be in possession of what he calls “the elephant gene.”
“Based on our observations, we want to attempt to develop a genetic tracer of cancer,” he said. The goal would be to eliminate the need for aggressive ALL treatment.
“I want to get to a point where we can scale back the massive amount of toxicity we are giving these young patients, some of whom don’t survive the treatment, much less the disease,” he said.
ALL is the most frequently occurring type of cancer in children. It was a devastating diagnosis in the 1960s and 1970s, but science has since made remarkable advances. Survivorship was once very low, but today, Müschen said, 90 percent of patients can be cured of ALL. He wants to ensure that those patients who become healthy, stay healthy – with no relapse.
“We are looking at the factors that cause relapse in children, and we want to find those patients that are more likely to experience relapse and get treatment therapy to them before that happens,” he said.
Müschen’s team has been together for 15 years. Most of his researchers followed him from USC to Children’s Hospital Los Angeles to University of California San Francisco to City of Hope, where they are convinced their groundbreaking research can best be nurtured and supported.
“City of Hope is the best place for us to put our ideas into practice and get them to patients as fast as we can,” Müschen said.