Drug Discovery, Delivery, and Translational Therapeutics Research Program

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PROJECT SUMMARY/ABSTRACT 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.