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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Finlay-Schultz, J; Cittelly, D M; Hendricks, P et al. (2015) Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene 34:3676-87
Alvarez-Calderon, Francesca; Gregory, Mark A; Pham-Danis, Catherine et al. (2015) Tyrosine kinase inhibition in leukemia induces an altered metabolic state sensitive to mitochondrial perturbations. Clin Cancer Res 21:1360-72
Kumar, Sushil; Raina, Komal; Agarwal, Chapla et al. (2014) Silibinin strongly inhibits the growth kinetics of colon cancer stem cell-enriched spheroids by modulating interleukin 4/6-mediated survival signals. Oncotarget 5:4972-89
Roth, Lauren W; Allshouse, Amanda A; Bradshaw-Pierce, Erica L et al. (2014) Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese and normal weight women. Clin Endocrinol (Oxf) 81:418-25
Roth, Lauren W; Bradshaw-Pierce, Erica L; Allshouse, Amanda A et al. (2014) Evidence of GnRH antagonist escape in obese women. J Clin Endocrinol Metab 99:E871-5
Colussi, Timothy M; Costantino, David A; Hammond, John A et al. (2014) The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA. Nature 511:366-9
Griesinger, Andrea M; Donson, Andrew M; Foreman, Nicholas K (2014) Immunotherapeutic implications of the immunophenotype of pediatric brain tumors. Oncoimmunology 3:e27256
Marek, Lindsay A; Hinz, Trista K; von Mässenhausen, Anne et al. (2014) Nonamplified FGFR1 is a growth driver in malignant pleural mesothelioma. Mol Cancer Res 12:1460-9
Holliday, Michael J; Zhang, Fengli; Isern, Nancy G et al. (2014) 1H, 13C, and 15N backbone and side chain resonance assignments of thermophilic Geobacillus kaustophilus cyclophilin-A. Biomol NMR Assign 8:23-7
Milgroom, Andrew; Intrator, Miranda; Madhavan, Krishna et al. (2014) Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent. Colloids Surf B Biointerfaces 116:652-7

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