Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 26¢ fertilized quail eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even the first to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in genetically-engineered mouse models of childhood cancer.
I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor our pediatric cancer researcher in training, Nicolle Hoffman. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 4 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but I also am a member of the Children’s Oncology Group committee that designs COG trial for rhabdomyosarcoma).
What's on the horizon? A lot! In moving to OHSU in Portland we're now teaming with Dr. Brian Druker to develop personalized targeted therapies (of the non-chemotherapy variety) for children with cancer. Our results can move faster than ever from the bench to the bedside with the COG Phase I pediatric oncology program here at our Doernbecher Children's Hospital, and with the leadership opportunity of building a de novo Pediatric Cancer Biology Program at OHSU, there's tremendous potential to build a focused team of laboratories that share a common goal of doing the best research and moving making results relevant to patients in the here and now.
Where there is a will, there is a way. Change can be tangible. And we are accountable.
Charles Keller, MD
keller@ohsu.edu
