The overall goal of the Developmental Therapeutics (DT) Program is to develop effecfive therapeutics for the treatment of cancer. The program is organized into four major interdisciplinary focus groups: Drug Discovery, Preclinical Development, Early Clinical Development, and Delivery. Interwoven within the four focus groups is a thematic emphasis on biomarkers and personalized medicine. Preclinical studies are conducted using novel model systems, pharmacology, and functional imaging so that appropriate biomarkers and patient selection criteria is incorporated into early clinical trials of targeted agents. Through close interactions between basic research laboratories, clinical scientists, the NCI, and the pharmaceutical industry, rapid development of new treatment and biomarker modalifies is being accomplished. Examples of these are the following contributions to the field made in the prior funding period: development of novel recombinant vaccines for the treatment of gastrointestinal cancer and hepatitis C (ongoing phase III trial);development of a human tumor explant models for predictive biomarkers for various targeted therapeutics; and evaluation of Stereotactic Body Radiation Therapy (SBRT) for metastases. Seminars, discussion groups, training, and courses are also provided to the members. Preclinical imaging capabilities have been expanded to include DCE-MRI, NMR/MRS, and PET. A radiochemistry program is being developed within the Colorado Translational Research Imaging Center (C-TRIC). The Phase I Unit has grown with >240 therapeutic enrollments in 2010 on >20 phase I trials which include pediatric and adult cancer patients. Many of these agents then move into the phase Ib/ll setting with the same investigators, with the implementation of biomarkers developed in member laboratories using preclinical models. The DT program consists of 63 full members from across the consortium, with a total of $21M in annual direct costs ($2.7M NCI). Since 2005, the per capita funding held by full members has increased by 67% from $197K to $329K. The DT program members produced 1,009 cancer-related publications from 2005-2010, an increase of 107%. Of these, 215 (21%) are inter-programmatic;199 (20%) are intra-programmatic;and 122 (12%) are both inter- and intra-programmatic publications for a total of 536 (53%) collaborative publications. Our goals for the next five years include faculty recruitment in the areas of leukemia/BMT in collaboration with the developing UCCC stem cell program;continued growth of trial enrollment, especially in investigator initiated studies;and expanded collaborations in novel imaging techniques.

Public Health Relevance

The Developmental Therapeutics Program (DT) fosters cancer-focused inter-disciplinary research among basic scientists and clinical researchers who are focused on the discovery, development and delivery of new anti-cancer therapies. The Program Leaders promote interaction and collaboration among DT members, which stimulates breakthroughs in diagnosis, treatment and prevention of cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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University of Colorado Denver
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Saichaemchan, S; Ariyawutyakorn, W; Varella-Garcia, M (2016) Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy. Curr Mol Med 16:40-62
Gillen, Austin E; Yamamoto, Tomomi M; Kline, Enos et al. (2016) Improvements to the HITS-CLIP protocol eliminate widespread mispriming artifacts. BMC Genomics 17:338
Justice, Cristina M; Bishop, Kevin; Carrington, Blake et al. (2016) Evaluation of IRX Genes and Conserved Noncoding Elements in a Region on 5p13.3 Linked to Families with Familial Idiopathic Scoliosis and Kyphosis. G3 (Bethesda) 6:1707-12
Eckwahl, Matthew J; Arnion, Helene; Kharytonchyk, Siarhei et al. (2016) Analysis of the human immunodeficiency virus-1 RNA packageome. RNA 22:1228-38
Iguchi, Nao; Malykhina, Anna P; Wilcox, Duncan T (2016) Inhibition of HIF Reduces Bladder Hypertrophy and Improves Bladder Function in Murine Model of Partial Bladder Outlet Obstruction. J Urol 195:1250-6
Seedorf, Gregory; Metoxen, Alexander J; Rock, Robert et al. (2016) Hepatocyte growth factor as a downstream mediator of vascular endothelial growth factor-dependent preservation of growth in the developing lung. Am J Physiol Lung Cell Mol Physiol 310:L1098-110
Agarwal, Neeraj; Dancik, Garrett M; Goodspeed, Andrew et al. (2016) GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis. Cancer Res 76:5175-85
Helfrich, Barbara A; Kim, Jihye; Gao, Dexiang et al. (2016) Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther 15:2314-2322
Munson, Daniel J; Egelston, Colt A; Chiotti, Kami E et al. (2016) Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR. Proc Natl Acad Sci U S A 113:8272-7
Scott, Aaron J; Lieu, Christopher H; Messersmith, Wells A (2016) Therapeutic Approaches to RAS Mutation. Cancer J 22:165-74

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