The Developmental Therapeutics for Solid Malignancies Program (DTSMP) has as its central role the improvement in curative therapy for children and adolescents with solid tumors. This objective is facilitated through multidisciplinary translational research, focusing on the identification of novel targets for therapy, understanding growth regulation of childhood solid tumors, mechanisms of drug action, drug resistance, diagnosis and clinical therapy. The program comprises 41 members (27 with primary appointments and 14 with secondary appointments) representing 11 academic departments St. Jude. Our preclinical studies range from development of high throughput screening to identify novel pharmacological probes to validate targets, mechanism based studies using genetically tractable organisms such as yeast for identifying drug targets, and repair processes associated with cytotoxic agents that damage DMA. Studies in mammalian cells involve in vitro culture to determine drug targets, and mechanisms of acquired and intrinsic resistance. In vivo models include panels of xenografts that represent common solid tumors in children and adolescents, and transgenic models produced by collaborators in other programs. The program has been productive with over 390 papers (88 intra-, 85 inter-programmatic), and has over $6.2 million in peer-reviewed grant funding supporting primary program members. The Program has continually fostered interactions among the basic laboratory investigations in molecular pharmacology, pharmacokinetics and clinical research to inform the design and conduct of clinical Phase l/ll trials. Over the past period of funding, the program has developed novel protocols for treatment of high-risk solid tumors such as advanced neuroblastoma, rhabdomyosarcoma, relapsed Wilms tumor and brain tumors. In addition, our studies with the camptothecins, the rapalogs, and other new agents have furthered our understanding on how better to use these agents in children. These protocols have been derived from fundamental studies within the program. In addition, ten St. Jude protocols have been extended to national trials in the Children's Oncology Group (COG). Information from the clinical trials allows further development and refinement of the preclinical research, leading ultimately to improved therapy. Preclinical and clinical studies will build on the current work with DMA topoisomerase I inhibitors, rapamycins, and start small molecule screens. We will continue to identify genes conferring drug resistance, and evaluate these agents with inhibitors of specific cellular signaling pathways. Studies outlined will develop novel anti-angiogenic approaches to tumor-selective therapy for treatment of high-risk neuroblastoma, and sarcomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA021765-33
Application #
8234127
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
33
Fiscal Year
2011
Total Cost
$522,001
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
ElInati, Elias; Russell, Helen R; Ojarikre, Obah A et al. (2017) DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line. Proc Natl Acad Sci U S A 114:12536-12541
Gibson, Todd M; Li, Zhenghong; Green, Daniel M et al. (2017) Blood Pressure Status in Adult Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study. Cancer Epidemiol Biomarkers Prev 26:1705-1713
Scott, Daniel C; Hammill, Jared T; Min, Jaeki et al. (2017) Blocking an N-terminal acetylation-dependent protein interaction inhibits an E3 ligase. Nat Chem Biol 13:850-857
Patel, Y T; Daryani, V M; Patel, P et al. (2017) Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas. CPT Pharmacometrics Syst Pharmacol 6:305-314
Penkert, Rhiannon R; Jones, Bart G; H├Ącker, Hans et al. (2017) Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines. Cytokine 91:1-5
Howell, Carrie R; Wilson, Carmen L; Ehrhardt, Matthew J et al. (2017) Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort study. Cancer :
Talleur, Aimee C; Triplett, Brandon M; Federico, Sara et al. (2017) Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-2, and Hapl Biol Blood Marrow Transplant 23:1910-1917
Wu, Jianrong (2017) Single-Arm Phase II Survival Trial Design Under the Proportional Hazards Model. Stat Biopharm Res 9:25-34
Svolos, P; Reddick, W E; Edwards, A et al. (2017) Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation. AJNR Am J Neuroradiol 38:1235-1241
Lin, Wenwei; Goktug, Asli N; Wu, Jing et al. (2017) High-Throughput Screening Identifies 1,4,5-Substituted 1,2,3-Triazole Analogs as Potent and Specific Antagonists of Pregnane X Receptor. Assay Drug Dev Technol 15:383-394

Showing the most recent 10 out of 6607 publications