The Drug Discovery, Delivery and Translational Therapeutics (DT) Program at the Markey Cancer Center (MCC) is scientifically focused on identifying novel targets and biomarkers and discovering and developing new drugs targeting these biomarkers. The MCC catchment area population has both a high cancer risk related to excessive carcinogen exposure and lack of access to cutting-edge clinical trials due to geographical isolation and poor socioeconomic status. The DT program vision is to understand the unique molecular and phenotypic markers of cancer in Kentucky as well as barriers to accessing care and integrate that knowledge to inform drug discovery, development, and delivery of early phase clinical trial efforts for a hard-to-reach Appalachian Kentucky population. MCC investigators are international leaders in biomarker discovery (Theme 1) with ongoing translational studies including more than 600 participants, evaluating the role of environmental carcinogens and identifying biomarkers of lung cancer. DT pharmaceutical scientists work to discover and develop new anticancer agents targeting identified mutations and phenotypes (Theme 2), partnering with Cancer Cell Biology and Signaling (CS) and Genomic Instability, Epigenetics, and Metabolism (GEM) program members. For example, a novel modulator of 4E-BP1 phosphorylation, a validated colon cancer target, was identified from the Appalachian natural products repository. DT investigators lead clinical trials focusing on cancers relevant to the catchment area (Theme 3) and have enrolled more than 500 patients to lung, colon and ovarian interventional treatment and diagnostic trials. They regularly partner with Cancer Prevention and Control (CP), CS and GEM program members to inform and advance MCC basic science, for example, translating early identification of the anticancer activity of PAR-4 in CS to clinical trials focused on a PAR-4 secratagogue. DT is a cross-disciplinary program of 47 investigators from 6 colleges and 18 departments who work together to develop novel anticancer therapies and translate these therapies into the clinic. This productive program has total annual external cancer-related funding of $8.5M ($5.9M annual direct costs, of which 28% is from the NCI). Members published 366 publications over the current funding period, 99 (27%) of which are inter-programmatic, 84 (23%) are intra-programmatic, and 189 (52%) are inter-institutional. The DT program Co-leaders, Drs. Jill Kolesar and Jon Thorson, have a long-standing collaboration and bring complementary expertise in biomarker discovery, drug development, and early clinical trials. Both direct key resources supporting the DT program, the MCC Precision Medicine Center and the UK Center for Pharmaceutical Innovation, respectively. Each leader brings critical strengths including local, national and international collaborations, entrepreneurial relationships, and active participation in NCI initiatives. Taken together, the DT program has a cohesive and collaborative team that translates novel biomarkers into targets for effective anticancer treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA177558-07
Application #
9741649
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40526
Liu, Jinpeng; Murali, Thilakam; Yu, Tianxin et al. (2018) Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky. Cancer Epidemiol Biomarkers Prev :
Ore, Robert M; Chen, Quan; DeSimone, Christopher P et al. (2018) Population-Based Analysis of Patient Age and Other Disparities in the Treatment of Ovarian Cancer in Central Appalachia and Kentucky. South Med J 111:333-341
Hubbard, W Brad; Harwood, Christopher L; Geisler, John G et al. (2018) Mitochondrial uncoupling prodrug improves tissue sparing, cognitive outcome, and mitochondrial bioenergetics after traumatic brain injury in male mice. J Neurosci Res 96:1677-1688
Alghamedy, Fatemah; Bopaiah, Jeevith; Jones, Derek et al. (2018) Incorporating Protein Dynamics Through Ensemble Docking in Machine Learning Models to Predict Drug Binding. AMIA Jt Summits Transl Sci Proc 2017:26-34
Wen, Yang-An; Xiong, Xiaopeng; Zaytseva, Yekaterina Y et al. (2018) Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis 9:265
Zhang, Hui; Fredericks, Tricia; Xiong, Gaofeng et al. (2018) Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Res 20:116
Zhong, Weixiong; Weiss, Heidi L; Jayswal, Rani D et al. (2018) Extracellular redox state shift: A novel approach to target prostate cancer invasion. Free Radic Biol Med 117:99-109
Xiong, Gaofeng; Stewart, Rachel L; Chen, Jie et al. (2018) Collagen prolyl 4-hydroxylase 1 is essential for HIF-1? stabilization and TNBC chemoresistance. Nat Commun 9:4456
Liu, Xinan; Yu, Ye; Liu, Jinpeng et al. (2018) A novel data structure to support ultra-fast taxonomic classification of metagenomic sequences with k-mer signatures. Bioinformatics 34:171-178
Al-Darraji, Ahmed; Haydar, Dalia; Chelvarajan, Lakshman et al. (2018) Azithromycin therapy reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction: Potential therapeutic targets in ischemic heart disease. PLoS One 13:e0200474

Showing the most recent 10 out of 359 publications