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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Harder, Bryan; Tian, Wang; La Clair, James J et al. (2017) Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog 56:1493-1500
Chen, Yufei; Anastassiadis, Konstantinos; Kranz, Andrea et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31:755-770.e6
DeRyckere, Deborah; Lee-Sherick, Alisa B; Huey, Madeline G et al. (2017) UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models. Clin Cancer Res 23:1481-1492
Scarborough, Hannah A; Helfrich, Barbara A; Casás-Selves, Matias et al. (2017) AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. Clin Cancer Res 23:1531-1541
Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773
Barón, Anna E; Kako, Severine; Feser, William J et al. (2017) Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. J Thorac Oncol 12:1512-1523
Todd, Maria C; Langan, Thomas A; Sclafani, Robert A (2017) Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. J Cancer 8:190-198
Brown, Dustin G; Borresen, Erica C; Brown, Regina J et al. (2017) Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. Br J Nutr 117:1244-1256
Haverkos, Bradley M; Abbott, Diana; Hamadani, Mehdi et al. (2017) PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 130:221-228
Shearn, Colin T; Saba, Laura M; Roede, James R et al. (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radic Biol Med 113:280-290

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