Bridge Grants Pick Up NIH Slack in Pediatric Cancer Research

Nick Mulcahy

April 19, 2012

April 19, 2012 — Three "bridge grants" have been awarded to American researchers of pediatric cancers in response to cuts in National Institutes of Health (NIH) funding, a private foundation announced.

The $100,000 grants allow the researchers to continue work while they reapply for funding, according to Alex's Lemonade Stand Foundation of Wynnewood, Pennsylvania.

A second set of grants is planned for the summer of 2012.

"With the amount of funding the NIH directs to childhood cancer continuing to be a concern, we want to be sure research moves forward, because the fact remains that children with cancer need new treatments now," Jay Scott, executive director of the foundation, said in a press statement.

The overall funding for pediatric research was an estimated 10% to 12% of all submitted grants to the NIH in 2012, leaving many projects unfunded, a spokesperson for the charity told Medscape Medical News.

Although many institutions have internal bridge-funding mechanisms, they are generally limited in their capacity; the bridge-grant program is novel among private charities, according to the foundation.

The recipients of the initial 2012 grants are Tom Look, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts; Kimberly Stegmaier, MD, also from Dana-Farber; and Adolfo Ferrando, MD, PhD, from the Columbia University Medical Center in New York City.

Dr. Look's work centers on improving targeted therapy for the high-risk subset of T-cell acute lymphoblastic leukemia (T-ALL).

The intensification of therapy for children with T-ALL has improved clinical outcomes substantially, but first-line therapy continues to fail in approximately 25% of children, according to Dr. Look. After initial failure, these patients have a very poor prognosis. This subset of children accounts for 62% of induction failures and 19% of relapses in pediatric T-ALL, he said.

Dr. Stegmaier's work involves targeting the EWS/FLI protein responsible for the development of Ewing's sarcoma, a pediatric solid tumor.

Such cancer-promoting, tumor-specific proteins have been considered "undruggable" — that is, difficult to target with traditional drugs, said Dr. Stegmaier in her project proposal.

"We will use a pipeline of innovative assays to identify compounds that inhibit...the EWS/FLI protein," she wrote. More broadly, the work aims to "develop a generic strategy for identifying chemical modulators of the myriad other 'undruggable' cancer-promoting proteins in pediatric malignancies," she wrote.

Dr. Ferrando's research focuses on a common activating genetic mutation, known as NOTCH1, in patients with T-ALL.

"The identification of activating mutations of NOTCH1 in over 50% of T-ALL has brought great interest to the development of targeted anti-NOTCH1 therapies," he wrote about his project.

Dr. Ferrando points out that early efforts to develop effective anti-NOTCH therapies have been hampered by a limited understanding of the target genes and oncogenic pathways controlled by NOTCH1 in T-ALL. "Our central hypothesis is that the aberrant activation of NOTCH1 signaling controls a complex transcriptional regulatory network responsible for the transformation of T-cell progenitor cells," he wrote.

He and his team expect that improved understanding of the oncogenic mechanisms downstream of NOTCH1 will result in improved anti-NOTCH1 targeted therapies in T-ALL.

Applicants for Alex's Lemonade Stand Foundation bridge grants must have projects that are focused on improving the diagnosis and cure rate of childhood cancers. According to the foundation, projects focused on complications from cancer treatments, quality of life, and care are not candidates for the bridge-grant category.

The foundation will only consider research projects that have been submitted and rejected by the NIH. To apply for a bridge grant, researchers should submit a cover letter, the original NIH application, a summary statement, a response to the NIH critique, and a budget. The guidelines for application submission can be found on the Alex's Lemonade Stand Web site.


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