Terrie G. Flatt, DO, MA
Director, Hematology & Oncology Spanish Language Clinic; Director, Hope Clinic; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full BiographyErin M. Guest, MD
Director, Cancer Genomics Program; Director, Cancer Center Biorepository; Associate Program Director, Pediatric Hematology/Oncology Fellowship; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full BiographyTomoo Iwakuma, MD, PhD
Director, Translational Oncology Research Laboratory; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine
Full Biography
Three Children’s Mercy investigators received new pediatric cancer research awards, totaling $700,000. The grants, independently awarded by Braden’s Hope for Childhood Cancer, will further collaborations with the University of Kansas Cancer Center to find better treatments and cures for childhood cancers.
Terrie Flatt, DO, MA, Hematology/Oncology/BMT, along with Andrew Godwin, PhD, University of Kansas Medical Center, received a three-year, $300,000 grant.
Erin Guest, MD, Hematology/Oncology/BMT, received a three-year, $300,000 grant.
Tomoo Iwakuma, MD, PhD, Hematology/Oncology/BMT, received a two-year, $100,000 grant.
Dr. Flatt and Dr. Godwin’s project, “Advancing New Treatment Options to Improve Outcomes of Children and Young Adults Diagnosed with Ewing Sarcoma,” will work to find drugs that destroy and prevent Ewing sarcoma (EWS) cancer cells from growing back.
The team will use their knowledge of the biology of this type of tumor to rationally combine drugs with like properties.
Based on the team’s findings, they will work with expert cancer physicians at Children’s Mercy and the KU Cancer Center to develop a clinical study to treat children and young adults with EWS that are not cured by standard chemotherapies.
The study will test multiple novel agents to develop treatments for EWS patients.
“We accepted this challenge, given no new therapies have been offered to children and young adults with EWS for nearly two decades,” the investigators wrote in their application. “This study will have a potential to offer new treatment options not typically afforded to patients with very rare tumors such as Ewing sarcoma.”
Co-investigators include Joy Fulbright, MD, Hematology/Oncology/BMT, and Joaquina Baranda, MD, Leonidas Bantis, PhD, and Vikalp Vishwakarma, PhD, all of the University of Kansas Medical Center.
Dr. Guest’s project, “Induced pluripotent stem cell models for pediatric KMT2A-r leukemia development and discovery of targeted therapies,” focuses on advancing therapies for children with leukemia in which the KMT2A gene is rearranged.
The team will investigate the cellular and molecular changes in novel engineered stem cell models of pediatric leukemia subtypes, and assess the response of three different KMT2A rearrangements to standard chemotherapy and novel agents.
“This study is the first of its kind, and we anticipate it will generate fundamental, mechanistic insight that can be shared with other researchers and will become widely used to study new treatments for leukemia involving KMT2A, in both children and adults,” Dr. Guest wrote.
Co-investigators include John Perry, PhD, Hematology/Oncology/BMT, and Jay Vivian, PhD, Clinical Genetics.
Dr. Iwakuma’s project, “Identifying compounds that target vulnerabilities imposed by EWS haploinsufficiency to discover novel treatments for EWSR1 fusion-positive childhood sarcomas,” will investigate if the less amount of Ewing sarcoma (EWS) protein is one of the causes for the disease progression of EWS-fusion sarcomas.
Based on the results of previous research the team has done, they hypothesize that the loss of single EWS gene in human cancer cells increases yet unappreciated cancer promoting signaling that is crucial for the survival of cancer cells with single EWS gene.
The goal of this study is to find drugs that specifically kill cancer cells with low EWS protein levels in EWS-fusion sarcomas, with sparing normal tissues and to understand the underlying mechanism. They will screen drug libraries to identify drugs/compounds that specifically kills cells with one EWS gene without killing cells with two EWS genes. They will investigate how the identified drugs affect cell death, cell cycle progression, DNA copy numbers, and molecular changes in the cell. Finally, they will investigate how the identified drugs inhibit the cancer progression following transplantation of Ewing sarcoma cells with one EWS gene into immunocompromised mice.
“Significance of this study is the new concept in which the drugs can specifically kill sarcoma cells with low EWS protein levels (with one EWS gene) with sparing normal cells with two EWS genes,” Dr. Iwakuma wrote. “Innovation of this study is that the drug will change the paradigm by reducing the side effects in the patients with EWS-fusion sarcomas.”
The ultimate goal is to increase the survival rate of patients with EWS-fusion sarcomas.
Co-investigators include Mizuki Azuma, PhD, and Anuradha Roy, PhD, both of the University of Kansas.