See also our related blog for the Pediatric Preclinical Testing Initiative.

Saturday, February 28, 2009

an informal word on the research in the Keller Laboratory

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, an orthopedic oncologist 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 25¢ fertilized chicken 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 starting 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 our novel mice.

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 my postdoctoral fellow, Koichi Nishijo. 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 3 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 we did present our results at a Children’s Oncology Group symposium a few weeks ago to help select a non-chemotherapy drug to add to the next COG trial for rhabdomyosarcoma).

We’re fortunate that despite the economic downturns that we’re doing pretty well so far… R01 funding from the National Cancer Institute, grants from the ALSF, the St Baldrick’s Foundation, the National Brain Tumor Society, the Joanna McAfee Foundation and more. Seven publications in print or accepted in 2008. This are truly exciting times. On top of all this is our mouse drug testing program mentioned above, which is open to public participation (for more details, see the left column of our blog). And just to put a plug in for a colleague’s new lab, try visiting Dr. David Langenau’s website . David has made a zebrafish model of embryonal rhabdomyosarcoma. He treats these little fish with drugs, right in the tank water. Also see Dr. Rene Galindo's website on using fruitflies to understand rhabdomyosarcoma. It will probably take a lot of new approaches and cooperation between groups to make the big impact we’re all hoping for, but it can be done.

Where there is a will, there is a way. Change can be tangible.

Charles Keller, MD

[ many thanks to collaborator Dr. Bryan W. Jones who took this picture on a hike in Utah. ]

Friday, February 27, 2009

GCCRI Symposium

In celebration of the 5th anniversary of the GCCRI we held a symposium on the Genetics and Biology of Childhood Cancer at the Hotel Contessa February 26 - 27th. Our founding director Dr. Sharon Murphy also attended (Sharon is now a Scholar-in-Residence at the Institute of Medicine). The Keller lab hosted the session on disease models and preclinical studies. Speakers in this session included Tom Look (DFCI) who gave a great talk on ALK that follows his Fall report in Nature, Rene Galindo spoke on drosophila models of alveolar rhabdomyosarcoma, Pat Reynolds talked about exciting new retinoid therapies for neuroblastoma and leukemia, and Peter Houghton reviewed the tremendous progress by the Pediatric Preclinical Testing Program. We can't thank the speakers enough for making this an exciting, interactive exchange.

Thursday, February 12, 2009

In memory of Patsy McCleish

Our deepest sympathies go out to Mandy and her sisters following the passing yesterday of their mother, Patricia Mary McCleish. Patsy was a loving mother and guiding example of strength throughout her many years of recurrent, metastatic cancer. Her positive attitude and love of life were an example to everyone who met her. Patsy's services will be held 1pm on Saturday February 14th at St. Francis of Assisi Church, 4201 De Zavala Rd, San Antonio. There will be a small gathering of family and friends at Mandy's home following the services.

The family asks that in place of flowers that a donation be made in her honor to the American Cancer Society to benefit research for lung or liver cancer.

Our hearts go out to Mandy and her sisters, Nicole Quirk and Allison McCleish, in this saddening time.

Saturday, February 7, 2009

Children's Oncology Group Conference on Rhabdomyosarcoma Biology

Koichi, Corrine and Charles attended the COG Rhabdomyosarcoma Biology Symposium on Feb 5-6 in Seattle. Charles presented our recent work on the rhabdomyosarcoma cell(s) of origin that Koichi has done, as well as results for new therapeutic targets and how to overcome drug resistance, which Corrine and Jinu have done. It was an exciting opportunity for researchers, clinicians and patient advocates (Joan Darling) to interact and exchange ideas. The rhabdomyosarcoma-specific symposium was conceived by Fred Barr (University of Pennsylvania) and implemented by Doug Hawkins (COG Soft Tissue Sarcoma Committee Chair, and faculty at Seattle Children's). While the weather in Seattle may have been typical for the season, the conference was very upbeat and there looks to be a new era of collaborative science on the horizon.