The Keller Laboratory at cc-TDI: Rhabdomyosarcoma Study published in Cancer Cell

Monday, February 14, 2011

Rhabdomyosarcoma Study published in Cancer Cell

In a report published today as the Featured Article in the journal Cancer Cell, investigators at the Oregon Health & Science University (OHSU) reveal interesting new findings for a kind of cancer called sarcoma. The most common sarcoma of children occurs in the muscle and has an appearance of muscle (rhabdomyosarcoma). In adults, sarcomas are often even more primitive appear (undifferentiated pleomorphic sarcoma). In their report, the Keller Laboratory reveals that childhood and adult sarcomas are linked in their biology, mutations and the cells from which these tumors first start.

Childhood muscle cancer, or rhabdomyosarcoma, is a condition that when spread throughout the body leads to a low survival rate – only 20 – 40%. In adults with soft tissue sarcomas, survival can be even lower. Now, for the first time, scientists and doctors know from where these tumors arise and what drives them to grow and spread. Armed with this new information, the researchers in the Pediatric Cancer Biology Program at OHSU are looking for ways to stop or eradicate these sarcomas.

“A commonly held belief is that cancers should be cut out, burned out or killed. There is a fourth option – to have cancer cells choose to become normal cells, in this case muscle cells,” says Dr. Keller, who led the study. “A least for a subset of patients, possibly the ones with hereditary cancer, one approach suggested by our research might be to administer drugs that muscle cancers to convert into non-cancerous muscle fibers. This is a minority opinion, but one held by a small group of careful scientists throughout the US and abroad.”

The survival rate for childhood muscle cancer that has spread has remained unchanged for more than 40 years. It has reached the point that increasing the intensity of chemotherapy, radiation or surgery is no longer having any improved effect. A novel approach taken by Keller and his colleagues in the laboratory as well as in new clinical trials is to use non-chemotherapy medicines to inhibit “molecular targets” such as growth factor receptors in this disease. Suman Malempati, Director of the Oncology Developmental Therapeutics Program at OHSU’s Doernbecher Children’s Hospital, is the lead on a national clinical trial of one such growth factor inhibitor. This study is the first trial to incorporate a molecularly-targeted drug into a clinical trial for childhood muscle cancer for the Children’s Oncology Group/Curesearch, a nationwide network of hospitals, doctors and leading scientists that develop new treatments for childhood cancer. This type of therapy tailored to a cancer’s mutation was first pioneered at OHSU by DeBakey-Lasker Award Recipient, Dr. Brian J. Druker. Dr. Druker and his colleagues developed a non-chemotherapy pill, Gleevec, which when taken each day causes a form of blood cancer, chronic myelogenous leukemia, to remain dormant indefinitely. Personalized Cancer Care for children and adults is the primary mission of the Knight Cancer Institute at OHSU.

We are grateful to the Scott Carter Foundation for the fellowship support of Jinu Abraham and Koichi Nishijo that has made these studies possible.

For the Preview commentary, click here.
For the Article itself, click go to the main page or here.

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You Can Participate in our Novel Therapeutics Studies !

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Children's Cancer Therapy Development Institute focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses 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. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

Our program is designed around community participation. Through the Children's Cancer Therapy Development Institute, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture {see 16 minutes onward}.)

For additional information regarding supporting this program please contact Charles Keller at charles@cc-tdi.org. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.