Lead Development and Optimization Shared Resource The Lead Development and Optimization (LDO) shared resource is a mission critical element of KUCC that allows us to redefine translational research in an academic cancer center. It is a key component of the Cancer Center's strategy to optimize the rapid movement of basic research findings into new therapeutic advances either through traditional lead compound development and optimization, or drug repurposing strategies. The LDO fosters translational research by: 1) providing support to researchers and clinicians engaged in the discovery and development of novel therapeutics for treatment and prevention of cancer, 2) providing drug discovery, delivery and development expertise to KUCC translational research projects, and 3) supporting key collaborations with industry, academic, government and disease philanthropy organizations with whom we have established collaborations in support of the goals and themes of our scientific research programs. The LDO, directed by Michael J. Baltezor, PhD, is a multi-component shared resource that provides unique expertise and capabilities in drug discovery, delivery, and development that is rarely available in an academic setting. Through a combination of highly trained, industry-experienced scientists and state-of the- art equipment the LDO is capable of supporting the development of novel cancer therapeutics in the following preclinical spaces: 1) Drug Discovery High Throughput Screening (HTS) - research and development focused on target selection and validation for high throughput method development and compound probe screening; 2) Drug Delivery Biotechnology Innovation and Optimization Facility (BIOF) - research and development focused on conventional and novel drug delivery and animal pharmacokinetic support; 3) Preclinical Proof of Concept (PPOC) - in vitro lead optimization and development of new and improved animal models for cancer to test lead molecules with capabilities to perform whole animal imaging in rodents. The LDO provided support for 51 research projects in 2010, 32 (62%) were led by KUCC members. During the past three years the LDO was instrumental in helping advance five drug therapies by KUCC investigators into Phase I clinical trials and to do so in a cost effective and efficient manner. Overall, Cancer Center members with peer-reviewed research funding used approximately 75% of the LDO's capacity.
The services provided by the LDO shared resource are available to researchers to facilitate the advancement of investigative drugs through the early stages of drug development. The skills necessary to conduct high throughput screening, drug delivery and preclinical proof of concept studies are not always easily available or affordable for academic investigators. The LDOSR addresses this need and allows investigators to concentrate on moving their research forward.
|Jiang, Yu; Simon, Steve; Mayo, Matthew S et al. (2015) Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors. Stat Med 34:613-29|
|Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R et al. (2014) Human cancer xenografts in outbred nude mice can be confounded by polymorphisms in a modifier of tumorigenesis. Genetics 197:1365-76|
|Winham, Stacey J; Armasu, Sebastian M; Cicek, Mine S et al. (2014) Genome-wide investigation of regional blood-based DNA methylation adjusted for complete blood counts implicates BNC2 in ovarian cancer. Genet Epidemiol 38:457-66|
|Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A et al. (2014) Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 23:1421-7|
|Pessetto, Ziyan Y; Ma, Yan; Hirst, Jeff J et al. (2014) Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor. Mol Cancer Ther 13:2276-87|
|Purrington, Kristen S; Slager, Susan; Eccles, Diana et al. (2014) Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis 35:1012-9|
|Bohl, Christopher R; Harihar, Sitaram; Denning, Warren L et al. (2014) Metastasis suppressors in breast cancers: mechanistic insights and clinical potential. J Mol Med (Berl) 92:13-30|
|Peterson, Kenneth R; Costa, Flávia C; Fedosyuk, Halyna et al. (2014) A cell-based high-throughput screen for novel chemical inducers of fetal hemoglobin for treatment of hemoglobinopathies. PLoS One 9:e107006|
|Meneely, Kathleen M; Luo, Qianyi; Riley, Andrew P et al. (2014) Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism. Bioorg Med Chem 22:5961-9|
|Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline et al. (2014) DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers. PLoS Genet 10:e1004256|
Showing the most recent 10 out of 26 publications