DEVELOPMENTAL THERAPEUTICS PROGRAM (Project-608) ABSTRACT Overview and Goals: The goal of the Developmental Therapeutics (DT) Program is to reduce the cancer burden through identification, development and testing of novel anticancer therapies and approaches. DT accomplishes this goal by hosting members with the required scientific expertise in the following areas: Target Inhibition and Companion Biomarkers, Drug Delivery, Radiation Biology and Delivery, Pharmacology, Stem Cells and Tumor Microenvironment, Immunotherapy, Preclinical Models and Imaging, Comparative Oncology and Clinical Trials. The program integrates this rich expertise into four major interdisciplinary focus groups (Drug Discovery, Preclinical Development, Early Clinical Development, and Delivery) that are linked by an overarching thematic emphasis on biomarkers and precision/ personalized medicine. Research Highlight: An example of the way the DT program takes laboratory studies forward to clinical testing is work from multiple DT members on Trametinib, a MEK1/MEK2 inhibitor, in patients whose tumors acquired resistance to BRAF inhibitor (J Clin Oncol, 20131; Lancet Oncol, 20122). Program Activities: Through stand-alone and intra-programmatic retreats, monthly meetings and a new grants program, the DT program promotes the transition of early findings through the therapeutic development process across the entire UCCC. For example, preclinical studies are conducted using novel model systems, pharmacology, and functional imaging allowing for the discovery of the appropriate biomarkers and patient selection criteria for incorporation into early clinical trials of targeted agents being tested pre-clinically. Through the establishment of close interactions between basic research laboratories, clinical scientists, the NCI, and the pharmaceutical industry, the DT leadership nurtures rapid development of new treatments and biomarkers. Members: The DT program has 111 members including 57 Full and 54 Associate members. The membership represents all 3 academic consortium institutions (University of Colorado Denver (UCD), University of Colorado Boulder (UCB), Colorado State University (CSU)) and are located in six different schools or colleges (Schools of Medicine, Pharmacy, Public Health, Liberal Arts at UCD; College of Arts and Sciences at UCB; College of Veterinary Medicine and Biomedical Sciences at CSU), and 18 departments. Current research funding is $18M. Peer-reviewed funding is $5.4M with $2.8M from the NCI and $2.6M from other peer sponsors. The DT Program produced 1,108 cancer-focused publications since the last review, of which 39% were inter- and 29% intra-programmatic, demonstrating the collaborative nature of the program. Future Directions: The program will enhance investigator initiated clinical trials (IITs) capitalizing on new investments by the UCCC that increase support for regulatory submissions and data management of IITs. The DT program will continue preclinical development of our own novel agents conceived within our program (e.g. SVC112, ONK101, neoamphimedine), and promote the identification of novel and efficacious drug combinations based on tumor molecular characteristics, biomarkers, and clinical testing of these therapies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA046934-33
Application #
10133561
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
1997-04-04
Project End
2022-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
33
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
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Cao, Shengya; Zhou, Keda; Zhang, Zhening et al. (2018) Constitutive centromere-associated network contacts confer differential stability on CENP-A nucleosomes in vitro and in the cell. Mol Biol Cell 29:751-762
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