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Children's Cancer Target of $1.73MM Grant

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Oct 4, 2013 1:00 AM

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Huntsman Cancer Institute at the University of Utah
Media Release

For Release:
October 4, 2013

Erica Neufeld
(240) 235-2201

Linda Aagard
Huntsman Cancer Institute
(801) 587-7639

Children's Cancer Target of $1.73MM Grant

Huntsman Cancer Institute Researchers to Test Targeted Treatment for Ewing Sarcoma

CureSearch for Children's Cancer this week awarded researchers at Huntsman Cancer Institute at the University of Utah a $1.73 million grant to test a novel targeted treatment for Ewing sarcoma that hopefully will disrupt the cancer's growth and spread. If successful, their work could lead to new treatment for the more than 250 children diagnosed with this rare cancer each year.

Ewing sarcoma is the second most common bone cancer in children and is a challenging cancer to treat because it has typically metastasized, or spread, by the time it is diagnosed. Further, once cancer has spread, many patients relapse after their initial chemotherapy and surgery. It is known that Ewing sarcoma occurs because of a chromosomal abnormality that causes an atypical protein, known as EWS/FLI, to be present (also called expressed), and that when EWS/FLI is expressed, literally thousands of genes are misregulated, leading to abnormal behavior.

The Huntsman Cancer Institute (HCI) researchers, led by Mary Beckerle, PhD, previously determined that EWS/FLI causes disruption of the internal cellular skeleton, which compromises the ability of the cells to adhere (stick) and remain in their normal environment. A cell that cannot remain in its normal environment is more likely to travel to another area of the body, facilitating the spread of the tumor. EWS/FLI also causes uncontrolled cell growth. Therefore, being able to stop, or block, EWS/FLI from changing a cell's adhesion might stop the spread of cancer.

Because it is difficult to directly inhibit EWS/FLI, Beckerle and the team are focused on a key regulator of EWS/FLI function, an enzyme called lysine specific demethylase (LSD1). Inhibitors of LSD1 represent a promising new treatment approach for Ewing sarcoma. In preliminary work in the HCI Center for Investigational Therapeutics (CIT), they used a computational chemistry approach to develop a molecule to inhibit (stop) LSD1. This agent displays potent anti-tumor activity when human Ewing sarcoma is implanted in mice. The LSD1 inhibitor reverses the effects of EWS/FLI and restores spreading and adhesion of the Ewing sarcoma cells, effects that the team proposes would prohibit the tumor cells from escaping and traveling to other areas of the body.

To expand their discovery with the goal of moving this approach into the clinic as a targeted therapy for Ewing sarcoma, they will evaluate the treatment effects of LSD1 inhibition--–alone or in combination with other medications in the form of preclinical trials. To do this, they will use a mouse model of metastatic Ewing sarcoma that mirrors the cancer in humans. At the same time, they will develop biomarkers and imaging tests to monitor responses to treatment and perform studies to assess the safety and toxicity of the new treatment, while determining appropriate dosing and timing which will serve as a guide when testing moves from the laboratory to patients.

Other team members on the project include: Stephen Lessnick, MD, PhD, a pediatric oncologist with a long standing program in Ewing sarcoma research; Sunil Sharma, MD, an oncologist with drug development and early phase clinical trial expertise in both the pharmaceutical and academic settings; and Alana Welm, PhD, a specialist in bone metastasis and development of predictive preclinical models. Other HCI collaborators are Lor Randall, MD, and Kevin Jones, MD, surgical oncologists; Mary Bronner, MD, pathologist; and John Hoffman, MD, molecular imaging specialist.

"We are excited that this research project is one of the three Acceleration Initiative grants we are awarding this year to researchers studying areas critical to achieving breakthroughs in treatments and with the potential to reach patients in early clinical trials within three years," says Laura Thrall, president and CEO of CureSearch. "We are thrilled to be funding research with patient-centric outcomes that not only addresses unmet needs but also uses innovative and novel approaches to do so."

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CureSearch for Children's Cancer is a national non-profit foundation whose mission is to fund and support targeted and innovative children's cancer research with measurable results, and be the authoritative source of information and resources for all those affected by children's cancer. CureSearch accelerates the cure by driving innovation, eliminating research barriers, and solving the field's most challenging problems; annually funding clinical trials and scientific research questions that challenge the status quo to push the field closer to a cure. Ultimately, CureSearch is working to change the odds for those children most at risk.

About Huntsman Cancer Institute at the University of Utah
Huntsman Cancer Institute (HCI) is one of the world’s top academic research and cancer treatment centers. HCI manages the Utah Population Database - the largest genetic database in the world, with more than 16 million records linked to genealogies, health records, and vital statistics. Using this data, HCI researchers have identified cancer-causing genes, including the genes responsible for melanoma, colon and breast cancer, and paraganglioma. HCI is a member of the National Comprehensive Cancer Network (a 23-member alliance of the world's leading cancer centers) and is a National Cancer Institute-Designated Cancer Center. HCI treats patients with all forms of cancer and operates several high-risk clinics that focus on melanoma and breast, colon, and pancreas cancers. The HCI Cancer Learning Center for patient and public education contains one of the nation's largest collections of cancer-related publications. The institute is named after Jon M. Huntsman, Sr., a Utah philanthropist, industrialist, and cancer survivor.