Childhood Cancer Research Program


To conduct translational and laboratory-based research to unveil the underpinnings of childhood cancer, and to extend these findings to the clinic in the form of better treatment for children with cancer.


Andrew Koh, M.D.
From left, research assistant Laura Coughlin, M.A.; Director of Pediatric Hematopoietic Stem Cell Transplantation Andrew Koh, M.D.; and Assistant Professor of Pediatrics Tiffany Simms-Waldrip, M.D., use an anaerobic chamber in a study of how the gut’s defense system fights off Candida albicans infection (see Fan et al., 2015).

The Childhood Cancer Research Program at the Simmons Comprehensive Cancer Center is focused on the discovery, investigation, and development of novel therapeutic strategies for children and adolescents with cancer—goals that program scientists are accomplishing through laboratory and clinical research. The roughly two dozen physicians and scientists in the program are engaged in collaborative clinical and basic/translational research that employs advanced molecular technologies and innovative model systems. Program researchers aim to quickly translate basic science findings to real-world clinical applications.

Recent discoveries include identifying previously unknown mutations (and possibly a new disease subclass) in Wilms tumor; demonstrating how the germs that normally live in the intestines may help to control the growth of the fungus Candida albicans, which can cause a life-threatening infection in children with leukemia, especially those undergoing stem cell transplant; and helping to identify a genetic anomaly that is a keystone in development of pediatric clear cell sarcoma of the kidney.

UT Southwestern’s main site to deliver pediatric hematology/oncology clinical care, the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Healthâ„  Children’s Medical Center Dallas, is one of the largest pediatric hematology/oncology programs in the U.S. and is internationally known as a center of excellence in clinical and laboratory research as well as patient care. The center provides children, adolescents, and young adults in North Texas access to standard as well as emerging therapies to fight pediatric cancer and blood disorders.

As just one example, in an effort spearheaded by Ted Laetsch, M.D., program scientists are conducting early-phase clinical trials testing new and promising therapies for an array of pediatric cancers including osteosarcoma, acute lymphoblastic leukemia, central nervous system and germ cell tumors, neuroblastoma, and medulloblastoma.


  • Uncovering the molecular drivers of childhood cancer through the use of sequencing, proteomics, and metabolomics studies
  • Tackling soft tissue, Ewing, and bone sarcomas with a multidisciplinary team approach deploying genomics, functional genomics, and clinical trials
  • Developing novel therapeutic opportunities through the creation and implementation of new childhood cancer models, including orthotopic patient-derived xenografts and non-mammalian genetic models in Drosophila and zebrafish
  • Maintaining a rich portfolio of clinical trial opportunities, ranging from investigator-initiated, early-phase trials based on scientific insights developed at UT Southwestern, to phase III studies conducted through the National Cancer Institute-funded Children’s Oncology Group
  • Realizing the potential of personalized therapies for childhood cancer through the use of molecularly targeted therapies and new approaches to activate the anti-cancer effects of the immune system

Research Highlights

Improving STS/ESFT survival. Supported by multi-investigator research funding at UT Southwestern of nearly $4 million from the Cancer Prevention and Research Institute of Texas, scientists on the childhood cancer team are leveraging state-of-the-art molecular biology and computing tools to sift through the array of genetic abnormalities associated with two kinds of cancers that commonly strike children and young adults, with the goal of revealing key mutations that drive tumor growth. The research, which encompasses collaborators in Houston and San Antonio and has a total budget of $6.9 million, focuses on soft-tissue sarcoma (STS) and the Ewing sarcoma family of tumors (ESFT), both of which often have poor outcomes despite aggressive, multimodal treatment. The project also will develop methods and processes to detect these genetic abnormalities in individual patients in the clinic, where physicians can choose treatments targeted specifically to counteract the cancer-promoting effects of the mutations.

Ewing’s Sarcoma Research Project. Funded by a $250,000 grant from the 1 Million 4 Anna Foundation, the childhood cancer research team has launched a new, multidisciplinary project to shed light on the disease’s genetic underpinnings. The project, led by James Amatruda, M.D., Ph.D., Associate Professor of Pediatrics, comprises five integrated research arms in an effort to identify molecular vulnerabilities that can be exploited in treating Ewing’s sarcoma, a malignant bone cancer that afflicts primarily adolescents and young adults. The bench-to-bedside research collaboration includes experts in molecular biology, cancer metabolism, gene regulation, genetic cancer models, and pediatric oncology.

DHART SPORE. Members of the childhood cancer team serve as project co-leaders and investigators within a National Cancer Institute-funded, multi-institution collaboration called the Developmental and HyperActive Ras Tumor (DHART) Specialized Program of Research Excellence, or SPORE. Focusing on tumors in patients with neurofibromatosis type 1, a heritable syndrome that elevates risk of specific tumors, especially in the young, the DHART program aims to implement new treatments targeting the effects of mutations of the NF1 tumor suppressor gene. The protein made by that gene interacts with key cancer-related genes called RAS, allowing the exploration of Ras-targeted therapies currently in development for a variety of cancers to be tested in tumors driven by NF1 mutations.

SPORE Overview
Research components and interactions within the Developmental and HyperActive Ras Tumor (DHART) SPORE (courtesy of Indiana University School of Medicine.

Members of the UT Southwestern team are focusing on developing better markers of early treatment response, as well as new targeted therapies, for children with malignant peripheral nerve sheath tumor (MPNST), a very aggressive soft tissue sarcoma, and on developing new insights about specific molecular vulnerabilities and targeted treatments for plexiform neurofibromas, which are nerve and soft-tissue tumors that can progress to MPNST. The SPORE is led by investigators at Indiana University and the University of California, San Francisco.

To Get Involved

The program seeks additional scientists and physicians who are interested in helping to eradicate childhood cancer through basic discovery and clinical translation of the most compelling scientific insights. Opportunities include new faculty appointments, post-graduate training positions, and scientific collaborations.

Contact Dr. Skapek for more details about the childhood cancer team, meetings, and more.

Selected Publications

Allen, C.E. et al. Target and agent prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH trial. J Natl Cancer Inst 109, djw274 (2016).

Amatruda, J.F. et al. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumorsBMC Cancer 13, 313 (2013).

Bowers, D.C. et al. Morbidity and mortality associated with meningioma after cranial radiotherapy: a report from the Childhood Cancer Survivor Study. J Clin Oncol 35, 1570-6 (2017).

Campbell, B.B. et al. Comprehensive analysis of hypermutation in human cancer. Cell 171, 1042-56.e10 (2017).

Chen, K.S. et al. EGF receptor and mTORC1 are novel therapeutic targets in nonseminomatous germ cell tumors. Mol Cancer Ther Feb 26 2018 [Epub ahead of print].

Chen, K.S. et al. A novel TP53-KPNA3 translocation defines a de novo treatment-resistant clone in osteosarcoma. Cold Spring Harbor Molecular Case Studies 2, a000992 (2016).

Drilon, A. et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378, 731-9 (2018).

Evageliou, N.F. et al. Polyamine antagonist therapies inhibit neuroblastoma initiation and progression. Clin Cancer Res 22, 4391-404 (2016).

Fan, D. et al. Activation of HIF-1alpha and LL-37 by commensal bacteria inhibits Candida albicans colonizationNat Med 21, 808-14 (2015).

Frankel, A.E. et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19, 848-55 (2017).

Hardy, K.K. et al. Neurocognitive functioning of children treated for high-risk B-acute lymphoblastic leukemia randomly assigned to different methotrexate and corticosteroid treatment strategies: a report from the Children's Oncology Group. J Clin Oncol 35, 2700-7 (2017).

Inskip, P.D. et al. Radiation-related new primary solid cancers in the Childhood Cancer Survivor Study: comparative radiation dose response and modification of treatment effects. Int J Radiat Oncol Biol Phys 94, 800-7 (2016).

Iqbal, N.S. et al. p19(Arf) limits primary vitreous cell proliferation driven by PDGF-B. Exp Eye Res 145, 224-9 (2016).

Kendall, G.C. and Amatruda, J.F. Zebrafish as a model for the study of solid malignancies. Methods in Molecular Biology 1451, 121-42 (2016).

Lee, E. et al. Genetic inhibition of autophagy promotes p53 loss-of-heterozygosity and tumorigenesis. Oncotarget 7, 67919-33 (2016).

Leger, K.J. et al. Circulating microRNAs: potential markers of cardiotoxicity in children and young adults treated with anthracycline chemotherapy. J Am Heart Assoc 6, e004653 (2017).

Liu, X. et al. In situ capture of chromatin interactions by biotinylated dCas9. Cell 170, 1028-43.e19 (2017).

Liu, X. et al. Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation. Nat Cell Biol 19, 626-38 (2017).

Lopez-Medina, E. et al. Candida albicans inhibits Pseudomonas aeruginosa virulence through suppression of pyochelin and pyoverdine biosynthesisPLoS Pathog 11, e1005129 (2015).

Lu, Z. et al. Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. Nat Med 23, 79-90 (2017).

Marina, N.M. et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. The Lancet Oncology 17, 1396-408 (2016).

Packer, R.J., et al. Pediatric low-grade gliomas: implications of the biologic era. Neuro Oncol 19, 750-61 (2017).

Rakheja, D. et al. Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumoursNat Commun 2, 4802 (2014).

Roy, A. et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidneyNat Commun 6, 8891 (2015).

Shaikh, F. et al. Paediatric extracranial germ-cell tumours. Lancet Oncol 17, e149-62 (2016).

Thienprayoon, R. et al. Perceptions of the pediatric hospice experience among English- and Spanish-speaking families. J Palliat Med 19, 30-41 (2016).

Tiwari, B. et al. Retrotransposons mimic germ plasm determinants to promote transgenerational inheritance. Curr Biol 27, 3010-6.e3 (2017).

Wilson, R.A. et al. Negative regulation of initial steps in skeletal myogenesis by mTOR and other kinases. Sci Rep 6, 20376 (2016).

Winick, N. et al. Impact of initial CSF findings on outcome among patients with National Cancer Institute standard- and high-risk B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. J Clin Oncol 35, 2527-34 (2017).

Wylie, A. et al. p53 genes function to restrain mobile elements. Genes Dev 30, 64-77 (2016).

Xu, L. et al. Potential pitfalls of mass spectrometry to uncover mutations in childhood soft tissue sarcoma: a report from the Children's Oncology Group. Sci Rep 6, 33429 (2016).

Zhang, Z.Z. et al. Glutathione depletion, pentose phosphate pathway activation, and hemolysis in erythrocytes protecting cancer cells from vitamin C-induced oxidative stress. J Biol Chem 291, 22861-7 (2016).