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
Hatfield, M Jason; Binder, Randall J; Gannon, Rowan et al. (2018) Potent, Irreversible Inhibition of Human Carboxylesterases by Tanshinone Anhydrides Isolated from Salvia miltiorrhiza (""Danshen""). J Nat Prod 81:2410-2418
Vo, BaoHan T; Kwon, Jin Ah; Li, Chunliang et al. (2018) Mouse medulloblastoma driven by CRISPR activation of cellular Myc. Sci Rep 8:8733
Shadrick, William R; Slavish, Peter J; Chai, Sergio C et al. (2018) Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors. Bioorg Med Chem 26:25-36
Ramsey, Laura B; Balis, Frank M; O'Brien, Maureen M et al. (2018) Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist 23:52-61
Churchman, Michelle L; Qian, Maoxiang; Te Kronnie, Geertruy et al. (2018) Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia. Cancer Cell 33:937-948.e8
Huang, I-Chan; Brinkman, Tara M; Mullins, Larry et al. (2018) Child symptoms, parent behaviors, and family strain in long-term survivors of childhood acute lymphoblastic leukemia. Psychooncology 27:2031-2038
Huang, I-Chan; Klosky, James L; Young, Chelsea M et al. (2018) Misclassification of self-reported smoking in adult survivors of childhood cancer. Pediatr Blood Cancer 65:e27240
Mandrell, Belinda N; Avent, Yvonne; Walker, Breya et al. (2018) In-home salivary melatonin collection: Methodology for children and adolescents. Dev Psychobiol 60:118-122
Drummond, Catherine J; Hanna, Jason A; Garcia, Matthew R et al. (2018) Hedgehog Pathway Drives Fusion-Negative Rhabdomyosarcoma Initiated From Non-myogenic Endothelial Progenitors. Cancer Cell 33:108-124.e5
Jones, Conor M; Baker, Justin N; Keesey, Rachel M et al. (2018) Importance ratings on patient-reported outcome items for survivorship care: comparison between pediatric cancer survivors, parents, and clinicians. Qual Life Res 27:1877-1884

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