Posted July 14, 2021

Eleanor Chen, M.D., Ph.D., University of Washington
Mei Zhang, Ph.D., Case Western Reserve University
Masanori Hayashi, M.D., University of Colorado at Denver
Steven Robinson, M.B.B.S., Mayo Clinic

The Peer Reviewed Cancer Research Program (PRCRP) is tasked by Congress to fund research that is relevant to Service Members and their families. For military families, a cancer diagnosis impacts the family, the Service Member’s unit, and overall mission readiness. A healthy family unit allows a Service Member to focus on their role in the overarching military mission. Beginning in fiscal year 2017 (FY17) Congress included Cancer in Children, Adolescents, and Young Adults as a topic area under PRCRP. Research within this topic area is targeted toward cancers that predominantly affect children (ages 0-14 years), adolescents (ages 15-24 years), and/or young adults (ages 25-39 years).^1,2 This topic area targets knowledge gaps in cancers that affect the military population, as 90% of military personnel and their family members are under the age of 39.³

Sarcomas are a heterogeneous group of over 80 different types of cancer that arise from mesenchymal or connective tissue. Sarcomas can be grouped into two main kinds: soft tissue sarcoma and bone sarcoma. The most common sarcomas in pediatric, adolescent, and young adult patients are rhabdomyosarcoma (median age at diagnosis = 17), synovial (median age at diagnosis = 39), osteosarcoma (median age at diagnosis = 22), and Ewing sarcoma (median age at diagnosis = 18).⁴ Depending on the stage, treatment for sarcoma can include surgery (amputation or wide local excision), radiation, and chemotherapy. These options can be life-altering for this population. Treatment for sarcoma is variable, and recurring or metastatic disease often has a poor outcome. Therefore, it is important to fund research that addresses the knowledge gaps in sarcoma, from biology and etiology of diseases to treatment that will increase survival rates. For FY20, the PRCRP funded two Impact Awards and two Idea Awards focused on sarcomas in pediatric, adolescent, and young adult patients.

Dr. Eleanor Chen

Enhancing the Efficacy of Precision Oncology-Based Therapy in Rhabdomyosarcoma
Eleanor Chen, M.D., Ph.D., University of Washington
Impact Award

Rhabdomyosarcoma (RMS) is a rare pediatric soft tissue cancer that develops from mesenchymal cells, the precursor cells for skeletal muscle. Current treatment options for RMS are surgery, chemotherapy and radiation with little success in improving outcomes, especially for patients with advanced disease. A major gap in RMS research is that functional roles of many of the mutated genes in RMS are not understood. Dr. Chen’s Impact Award will use a zebrafish model of RMS which allows for a cost-effective, high-throughput functional analysis of candidate genes in vivo. Near-term outcomes of this project will inform rational design of future clinical trials with therapeutic agents to target relevant mutations.

Dr. Mei Zhang

BG34-200 Triggers Myeloid Recruitment and M1 Reprogramming to Enhance Immunotherapy for Pediatric and AYA Osteosarcoma
Mei Zhang, Ph.D., Case Western Reserve University
Impact Award

Osteosarcoma (OS) is an aggressive malignant bone cancer affecting children, adolescents, and young adults, with about 400 to 1,200 new cases a year in the United States. The outcome for metastatic OS remains poor despite aggressive chemotherapy and surgery regimens. Recent advances in immune therapy have resulted in renewed hopes for OS. However, the tumor microenvironment of OS is heavily infiltrated with suppressive myeloid cells, which prevents an effective anti-tumor immune response. This suggests that targeting suppressive myeloid cells could be a novel approach to treating OS. Dr. Zhang’s group has shown that a novel oat-derived glucan compound, BG34-200, targets myeloid cells and switches them to a stimulating rather than suppressive phenotype. Her Impact Award will study the efficacy of BG34-200 in an animal model of osteosarcoma in order to support progression toward a Phase I clinical trial to treat metastatic OS patients.

Dr. Masanori Hayashi

Identification of Drivers of Metastasis-Initiating Cells in Ewing Sarcoma
Masanori Hayashi, M.D., University of Colorado at Denver
Idea Award

The current treatment strategy for Ewing sarcoma (ES) consists of high doses of toxic chemotherapeutic drugs. Despite this intense regimen, outcomes are still poor for patients with advanced disease. The prevention and treatment of metastatic disease is a major gap in ES research. ES is driven by the aberrant fusion transcription factor EWS/Fli1, but it is unknown how EWS/Fli1 drives metastatic progression. Dr.Hayashi’s Idea Award will test the hypothesis that heterogeneous activation of EWS/Fli1-regulated genes drives the rise of metastasis-initiating cells within the local tumor as well as the growth of metastatic cells within the lungs. By understanding which cells in the tumor give rise to metastasis, it may be possible to identify therapeutic targets for metastatic ES.

Dr. Steven Robinson

Targeting Synovial Sarcoma with Cancer Testis Antigen Incorporated Oncolytic Viruses
Steven Robinson, M.B.B.S., Mayo Clinic
Idea Award

Synovial sarcoma (SS) is an aggressive type of soft tissue sarcoma that disproportionately affects the young adult population. SS is characterized by high expression of cancer testis antigens (CTAs) such as NY-ESO-1. However, strategies to target these antigens have been largely unsuccessful, perhaps due to a tumor microenvironment lacking immune cell infiltration. Dr. Robinson’s Idea Award aims to develop a novel oncolytic virus vaccine targeting NY-ESO-1 and an immune stimulator neutrophil activating protein (NAP). Additionally, the vaccine will be tested in combination with immune checkpoint inhibitors, which SS has previously been resistant to, in order to improve outcomes for SS patients.

Links to abstracts will be available at https://cdmrp.health.mil/search.aspx.

References:

¹ National Cancer Institute. Cancer in Children and Adolescents. https://www.cancer.gov/types/childhood-cancers/child-adolescent-cancers-fact-sheet.

² National Cancer Institute. Adolescents and Young Adults with Cancer. https://www.cancer.gov/types/aya.

³ United States Department of Defense. 2019 Demographics Profile of the Military Community. https://www.militaryonesource.mil/data-research-and-statistics/military-community-demographics/

⁴Gage MM, Nagarajan N, Ruck JM, et al. 2019. Sarcomas in the United States: Recent trends and a call for improved staging. Oncotarget 10(25):2462-2474. doi: 10.18632/oncotarget.26809. PMID: 31069009; PMCID: PMC6497437.