New concept for the drug resistance in aggressive cancer in childhood

Researchers at Oregon Health & Science University thorn Cup of children's Hospital have identified known a promising new approach to overcome resistance in children with an extremely aggressive muscle cancer as Rhabdomyosarcoma, alveolar. Their results are published online this week in the journal of Molecular Cancer Therapeutics and will be featured on the cover of the print issue of the magazine.

Rhabdomyosarcoma makes more than 50 percent of all soft tissue cancers in children. After extensive treatment, the survival rate in Rhabdomyosarcoma, alveolar patients with advanced disease is less than 20 percent. Results as they are, what researchers in Pediatrics keep cancer biology program at OHSU thorn Cup a breakthrough work around the clock in the direction of dismal.

"Despite our efforts, results for metastatic Rhabdomyosarcoma, have improved alveolar not for decades." That is why our results are of importance. Our clinical partners now have a new method of resistance to the current treatment for cancer in childhood muscle damage be border, "said Jinu Abraham, PhD., associate principal author and senior researcher in the pediatric cancer biology program on OHSU thorn Cup and a member of the OHSU Knight Cancer Institute."

Previous studies under the direction of Charles Keller, m.d., Director of pediatric cancer biology program at OHSU thorn Cup, showed an important relationship between increased growth factor signaling by insulin-like growth factor receptor (Igf1r) and decreased survival in children with Rhabdomyosarcoma, alveolar, a rare form of muscle cancer, which occurs in the limbs, chest or abdomen of children and young people. Growth factor signaling is required for normal development but impairment of this option causes, that abnormal cell growth.

In the current study, Abraham and colleagues tested whether the non-chemotherapeutic agent NFA AEW541 could stop, Igf1r signal in a novel mouse model genetically so that Rhabdomyosarcoma, alveolar tumors start and expand in the same places that they are found in children. Her research showed that blocks not chemotherapy tumor progression in 33 percent of mice with tumors, but most of the mice developed resistance to the drug.

To reveal the reason for resistance, partner led the researcher additional experiments, the Igf1r with an other tumor surface enzyme known as HER2, showed the tumor growth despite the growth-inhibiting drug fueled.

"Fortunately, if we constantly Rhabdomyosarcoma cells with a combination of the Igf1r inhibitor and HER2 inhibitor lapatinib, there was a significant increase in the tumor cell killing compared to either alone, drug", said Abraham. "Our study has shown that both Igf1r and HER2 might very promising approach to the prevention of resistance to Igf1r-inhibiting drugs in Rhabdomyosarcoma."

"Understand why some Rhabdomyosarcoma are resistant tumors against Igf1r inhibitors be sure the study of these drugs in the clinical setting." "This discovery in the laboratory gives us an option for the attempt to overcome this resistance and leads, as we combined these new targeted therapies for the treatment of patients with cancer,", said Suman Malempati, m.d., co-author of the recent study and principal investigator for the first national clinical trial receptor Igf1 in combination with chemotherapy in patients with metastatic Rhabdomyosarcoma inhibitor.

The children Oncology Group (COG) trial, now at OHSU thorn Cup of children's Hospital and several other COG Web sites, the first is in North America, one molecular targeted drug in a clinical trial for cancer in childhood muscle to integrate.

Notes:

National Cancer Institute, Scott Carter Foundation, Alex's lemonade stand Foundation and the Hyundai hope on Wheels program funded the current study "evasion mechanisms Igf1r inhibition in Rhabdomyosarcoma."

Jinu Abraham, PhD., is a senior of researcher and Scientific Director of Pediatric non-clinical testing initiative to the pediatric cancer biology program, Pape family Pediatric Research Institute, OHSU thorn Cup of children's Hospital; and a member of the OHSU Knight Cancer Institute.

Charles Keller, m.d., is the leader of the pediatric cancer biology program in the Pape family Pediatric Research Institute and associate professor of Pediatrics (Hematology/Oncology) OHSU thorn Cup of children's Hospital; and a member of the OHSU Knight Cancer Institute and the Oregon stem cell Center at OHSU.

Suman Malempati, m.d., is an Assistant Professor of Pediatrics (Hematology/Oncology) and Director of the Oncology developmental Therapeutics program OHSU thorn Cup children's Hospital; and a member of the OHSU Knight Cancer Institute.

Source:
Tamara Hargens-Bradley
Oregon Health Sciences & University