Corinne Linardic, MD, PhD, associate professor of pediatrics and pharmacology and cancer biology, and Christopher Counter, PhD, George Barth Geller Distinguished Professor of Pharmacology, professor of pharmacology and cancer biology, and assistant professor in radiation oncology, are leading a team that has been awarded a federal grant to study one of the least-understood but most-fatal forms of childhood cancer, fusion-positive alveolar rhabdomyosarcoma (ARMS).

Taking a moonshot at a rare childhood cancer

The $5.8 million, five-year grant is part of the Cancer Moonshot Initiative, a National Institutes of Health program dedicating $1.8 billion over seven years to accelerating the discovery of new ways to prevent, diagnose, and cure cancer. The Duke FusOnC2 Center has an innovative team and dynamic environment in which data interpretation is informed by complementary technological approaches and by biological and clinical knowledge. This comprehensive approach will transform understanding of PAX3-FOXO1-mediated oncogenesis and create opportunities for therapeutic intervention. The Center’s overarching goal is to advance the therapeutic tractability of the PAX3-FOXO1 fusion protein in ARMS by comprehensively identifying the druggable co-regulators, modulators, and intrinsic activities of PAX3-FOXO1. The Duke Center will be part of an international team led by researchers from the Broad Institute, the Massachusetts Institute of Technology (MIT), Harvard University, Duke University, and the National Cancer Institute.

ARMS, a cancer with features of skeletal muscle, is rare, accounting for about 1 percent of all cancers among children and adolescents, and an annual incidence that is truly “one in a million.” It is also deadly: The overall survival rate for fusion-positive ARMS is 30 percent, with less than 10 percent survival rate for patients whose cancer has metastasized. Currently, there are no ARMS-specific therapies available. As a poorly understood “orphan disease,” it would be difficult for the pharmaceutical industry to undertake the costly development of new treatments for such a small pool of patients.

This grant will enable Linardic and her team to make significant strides toward improving understanding of the molecular underpinnings of fusion-positive ARMS and identifying compounds that could be developed into new treatments.

Project Title: Defining and targeting the molecular vulnerabilities of the PAX3-FOX01 protein in rhabdomyosarcoma
Project Number: 1U54CA231630-01A1
Contact PI/Project Leaders: Corinne M. Linardic
Awardee Organization: Duke University
[Scientific Abstract]