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Pediatric Hematology and Oncology Research
The Division of Pediatric Hematology and Oncology is nationally distinguished for its design and conduct of NIH-funded multicenter clinical trials involving childhood cancer and blood disease.
Dr. Ted Laetsch
Dr. Andrew Koh's Lab
Laboratory Research
Faculty are conducting molecular and cellular biology experiments in cancer and blood disease. Laboratory research efforts are both basic and translational studies that help to bridge the lab and clinical venues. Research is carried out in laboratories in the Division of Hematology/Oncology and also across the entire UT Southwestern Medical Center campus, including the NCI-designated Simmons Cancer Center and the Children's Medical Center Research Institute at UT Southwestern.
Active areas of basic research include:
Using fruit fly and zebrafish models to understand the genetic defects causing rhabdomyosarcoma, Ewing sarcoma, and malignant germ cell tumor
Using complementary pre-clinical models to dissect the key "vulnerabilities" in rhabdomyosarcoma, Ewing sarcoma, and other soft tissue sarcomas
Understanding the molecular machinery by which normal cells can undergo "senescence" as a tumor suppressor mechanism in the presence of a cancer-causing oncogene
Identifying novel proteins that can be "targeted" as novel therapies in childhood cancer
Understanding how certain cancer-causing mutations influence the metabolism in childhood brain tumors and certain types of sarcoma
Uncovering how hematopoietic and embryonic stem cells are controlled and how these control mechanisms can go awry in cancer and blood disease
Elucidating the molecular machinery that guides erythrocyte development
Using novel model systems to elucidate the host and bacterial factors that cause invasive bacterial and fungal infections
Physicians in the Division are engaged in a wide range of clinical research efforts spanning the cancer and blood disease programs. Clinical research efforts are supported by robust infrastructure provided by the Clinical Research Office (CRO) within the Gill Center and the Simmons Comprehensive Cancer Center at UT Southwestern, the only NCI-designated cancer center in North Texas. At any point, 75 to 100 oncology trials and 20 to 30 hematology trials are open for enrollment for Gill Center patients.
Active areas of clinical research include:
Prospective clinical trials for children with cancer, conducted under the umbrella of the NCI-sponsored Children's Oncology Group
Prospective, early-phase clinical trials for children with hematological malignancies, conducted as part of the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium and other academic and industry partners
Prospective therapeutic trials for children with sickle cell disease, iron deficiency anemia, and hemophilia
Investigator-initiated and industry-sponsored therapeutic studies of children with cancer and blood disease
Retrospective research studies investigating molecular and clinical factors influencing late effects in childhood cancer survivors
Prospective and retrospective studies assessing a variety of quality measures of children with chronic hematology disorders
Early phase clinical trials of immunotherapeutics for childhood cancer, including the use of CAR T-cells for childhood leukemia
Prospective and translational research trials in children with venous thrombosis
Clinical and laboratory research efforts are funded by a wide variety of national, regional and local organizations, such as the National Cancer Institute, the National Heart, Lung, and Blood Institute, National Eye Institute, Cancer Research and Protection Institute of Texas, American Cancer Society, St. Baldrick's Foundation, Children's Cancer Fund of Dallas, Children's Medical Center Foundation, Wipe-Out Kids' Cancer, the 1 Million for Anna Foundation, and Hyundai Hope on Wheels Foundation.
September 11, 2018 - $37 million CPRIT support includes funds for pediatric cancer database
The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded more than $37 million to UT Southwestern for cancer research and prevention, including more than $5 million to create a platform for collecting pediatric cancer data across multiple institutions. Because childhood cancers are rare, multi-institution research studies are necessary and UT Southwestern will lead in this pooling effort.
The CPRIT grant includes an award of $5,394,842 to Dr. Yang Xie, Associate Professor of Clinical Sciences and of Bioinformatics, and Dr. Stephen Skapek, Chief of Pediatric Hematology/Oncology, to develop a pediatric cancer data base and support system.
"The most effective research includes clinical, genomic, and imaging data from historical and prospective trials across multiple institutions, however inconsistent terminology and other issues often hamper researchers' efforts to combine data. Our goal is to break down these academic silos and create a broad database that will benefit all," said Dr. Xie.
The Pediatric Cancer Data Core will develop a system and computational tools for collecting and integrating data from clinical trials, electronic health records, molecular and imaging studies, and tissue banks. The system will become a resource for all Texas childhood cancer programs. Read the whole story.
August 29, 2018 - New test uncovers metabolic vulnerabilities in kidney cancer
In order to halt the growth of cancer cells, you have to know what feeds them. Researchers at the nationally recognized Kidney Cancer Program at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center have developed a novel approach using glucose that may open up new opportunities for therapeutic intervention.
"Not long ago, most cancer biologists thought that glycolysis, the partial degradation of glucose to lactate, was an essential feature of aggressive tumors. This idea persisted for a century despite the fact that it was based entirely on analyzing cancer cell metabolism outside of the body," said Dr. Ralph DeBerardinis, Professor of Pediatrics and at the Children's Medical Center Research Institute at UT Southwestern and a Howard Hughes Medical Institute Investigator. Read the whole story.
August 1, 2018 - UT Southwestern Scientists Identify New Mechanisms Underlying Pediatric Kidney Cancer
Connecting two previously unrelated insights about the formation of pediatric kidney cancer, researchers at UT Southwestern Medical Center have uncovered the means by which the cancer continues to grow, providing potential targets for more effective treatments in the future. Wilms tumor is the most common cancer of the kidney in children. Typically, the disease is treated with surgery, radiation, and chemotherapy. This combination is effective for many patients but has numerous side effects, and a cure remains elusive for those with aggressive disease. This situation has driven investigators at UT Southwestern to look for more effective and less toxic ways to treat Wilms tumor.
Previously, pediatric investigators from the nationally recognized Kidney Cancer Program at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center identified a new molecular subset of Wilms tumors driven by recurrent mutations at "hot spot" residues in genes of the microRNA (miRNA) processing pathway (Rakheja et al., Nat Comm, 2014). A miRNA is a tiny RNA that reduces the production of specific proteins in cells. Nevertheless, it was unclear exactly why impairment of miRNA function caused Wilms tumors.
Dr. James Amatruda, former Associate Professor of Pediatrics, Molecular Biology, and Internal Medicine, along with Dr. Kenneth Chen, Instructor of Pediatrics, steered the study published in Genes and Development. Read more
June 5, 2018 - A Popular Aquarium Fish May Hold Answers to How Tumors Form in a Childhood Cancer
Muscle precursor cells called myoblasts are formed during normal fetal development and mature to become the skeletal muscles of the body...
Cancer researchers at UT Southwestern Medical Center developed a zebrafish model for the childhood cancer. To do this, Dr. James Amatruda's lab inserted the human PAX3-FOXO1 gene into the DNA of zebrafish. Using this new transgenic zebrafish, the researchers showed that the fused-gene DNA causes rhabdomyosarcoma that is similar to the human disease. They found it does this by turning on another gene, HES3, which leads to overproduction of the skeletal muscle precursor cells and allows for PAX3-FOXO1+ cells to survive during development instead of dying. Read more
February 21, 2018 - Drug targeting mutant cancer gene is highly effective, durable
A drug targeting a gene fusion that occurs in lung, colon, and other cancers was effective in 75 percent of patients of all ages in clinical trials, and an even higher percentage of pediatric patients, researchers at UT Southwestern's Simmons Cancer Center announced. The drug is being given fast-track consideration by the Food and Drug Administration.
The drug, larotrectinib, targets TRK-fusion, which can occur in lung, colon, thyroid, and many other types of cancer, said Dr. Ted Laetsch of UT Southwestern's Department of Pediatrics and the Harold C. Simmons Comprehensive Cancer Center. Dr. Laetsch led the pediatric arm of the clinical trial for the study, which appears in the New England Journal of Medicine. Read more
February 14, 2018 - CART-T clinical trial enrolling multiple myeloma patients
UT Southwestern Medical Center is one of nine exclusive sites in the country enrolling multiple myeloma patients for a clinical trial of the CAR-T "living drug" therapy for cancer. CAR-T therapy (chimeric antigen receptor T-cell therapy) is an innovative immunotherapy that uses a re-engineered version of the patient's own immune cells to fight cancer. A UT Southwestern cancer researcher who was among the first patients to be treated, has now been cancer-free for two years.
As one of just 49 in the country designated a Comprehensive Cancer Center by the National Cancer Institute and the only one in North Texas, UT Southwestern's Harold C. Simmons Comprehensive Cancer Center is offering both treatments and clinical trials in several critical areas:
Dr. Ted Laetsch, Assistant Professor of Pediatrics, led the only clinical trial site in the Southwest for a CAR-T treatment for acute lymphoblastic leukemia (ALL). Results from the trial resulted in FDA approval for the first CAR-T therapy, and Dr. Laetsch is now treating ALL patients who are 25 and under with this CAR-T therapy at the Pauline Allen Gill Center for Cancer and Blood Disorders at Children's Health.
In November, the FDA approved a CAR-T treatment for lymphoma, and UT Southwestern physicians soon will be offering this treatment to patients through the Bone Marrow Transplantation/Hematologic Malignancies Clinic at the Simmons Cancer Center.
As new uses for CAR-T continue to be explored, leadership and guidance on how and when to use these treatments also is needed. Dr. Ankit Kansagra, Assistant Professor of Internal Medicine, is co-leader of the Global CAR-T Initiative, a group of physicians who are meeting to draw up guidelines for CAR-T use. Read more
February 1, 2018 - Simmons Cancer Center researchers part of historic CAR-T breakthrough
A historic study involving researchers from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center demonstrates the effectiveness of CAR-T therapy, which uses genetically modified immune cells to treat acute lymphoblastic leukemia (ALL) in children and young adults. The research appears in the New England Journal of Medicine. Dr. Ted Laetsch served as the lead investigator for the only clinical trial site in the Southwest for the CAR-T trial. Read more
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