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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McCubbrey, Alexandra L; Barthel, Lea; Mohning, Michael P et al. (2018) Deletion of c-FLIP from CD11bhi Macrophages Prevents Development of Bleomycin-induced Lung Fibrosis. Am J Respir Cell Mol Biol 58:66-78
Fitzpatrick, Rikki L; Quimby, Jessica M; Benson, Kellyi K et al. (2018) In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease. J Vet Intern Med 32:1951-1957
Lee, Kyubum; Kim, Byounggun; Choi, Yonghwa et al. (2018) Deep learning of mutation-gene-drug relations from the literature. BMC Bioinformatics 19:21
Roof, Allyson K; Jirawatnotai, Siwanon; Trudeau, Tammy et al. (2018) The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine. Endocrinology 159:2421-2434
Kimball, Abigail K; Oko, Lauren M; Bullock, Bonnie L et al. (2018) A Beginner's Guide to Analyzing and Visualizing Mass Cytometry Data. J Immunol 200:3-22
Parrish, Janet K; McCann, Tyler S; Sechler, Marybeth et al. (2018) The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell proliferation and survival, and reduced tumor growth. Oncotarget 9:33110-33123
Herbst, Roy S; Redman, Mary W; Kim, Edward S et al. (2018) Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol 19:101-114
Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P et al. (2018) Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms. PLoS One 13:e0193499
Nemkov, Travis; Sun, Kaiqi; Reisz, Julie A et al. (2018) Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage. Haematologica 103:361-372
Soontararak, Sirikul; Chow, Lyndah; Johnson, Valerie et al. (2018) Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model. Stem Cells Transl Med 7:456-467

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