PROJECT-004: MOLECULAR CARCINOGENESIS AND CHEMOPREVENTION PROGRAM (MCC) PROJECT SUMMARY / ABSTRACT The Molecular Carcinogenesis and Chemoprevention (MCC) Program, led by Steven K. Clinton, MD, PhD, has a collaborative team of 37 basic, translational and clinical scientists. These faculty have appointments in 17 Departments/Divisions within the Colleges of Medicine, Arts and Sciences, Pharmacy, Food Agriculture and Environmental Sciences, Public Health, Dentistry, Education and Human Ecology and Veterinary Medicine.
The Specific Aims of the MCC Program are: 1) to characterize molecular and cellular changes induced by chemical, physical, hormonal and infectious agents that contribute to neoplastic transformation and multistage carcinogenesis in experimental models and humans; 2) to develop and characterize novel agents for cancer chemoprevention and define their efficacy, safety, and mechanisms of action using in vitro and preclinical models; and 3) to identify dietary and nutritional components that may enhance or inhibit the carcinogenesis cascade across the continuum of cancer progression. Each of these aims results in translational prevention studies in human populations with an emphasis on those at risk due to exposure to carcinogenic or cancer promoting agents, familial and genetic predisposition, or due to the presence of premalignant lesions. The MCC Program's overarching goals, implemented through multiple MCC initiatives, are to accelerate the research objectives of each Aim through incentivizing and stimulating collaborative investigation among MCC members, other investigators of the OSUCCC as well as facilitating the implementation of translational studies of cancer etiology, prevention, and progression in human trials. The MCC enhances quality by promoting knowledge of and utilization of state-of-the-art technologies provided by the OSUCCC shared resources (members utilize 14/14 shared resources). The MCC Program, during its previous review (2004-2009) was graded as ?Outstanding to Exceptional?. During this funding period (2009-2014), MCC Program members published 484 cancer relevant peer-reviewed articles in top tier journals for the respective fields of carcinogenesis, chemoprevention, and nutrition. Collaboration is extensive with 28% intra-programmatic publications and 55% inter-programmatic publications, with 272 or 56% being multi-institutional and 447 or 92% being collaborative publications. Peer-reviewed funding for the MCC Program is $5.19M in annual direct costs with $2.9M (56%) from the NCI. Translational research has been robust as well with 20 human trials led by MCC members employing the OSUCCC Clinical Trials Office resulting in 360 interventional accruals during the last funding cycle, 72% of which were from investigator-initiated Phase I and II trials. The current MCC Program uniquely integrates investigators across disciplines yet with shared interests focusing upon the interactive themes of carcinogenesis, chemoprevention, and nutrition. Our future goals include the integration of new initiatives involving the microbiome and metabolomics, two areas benefiting from rapid growth in technology and bioinformatics that will dramatically impact our understanding of carcinogenesis and strategies for cancer prevention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016058-44
Application #
9843884
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
44
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Baldassari, Federica; Zerbinati, Carlotta; Galasso, Marco et al. (2018) Screen for MicroRNA and Drug Interactions in Breast Cancer Cell Lines Points to miR-126 as a Modulator of CDK4/6 and PIK3CA Inhibitors. Front Genet 9:174
Yang, Xiaosong; Pan, You; Qiu, Zhaojun et al. (2018) RNF126 as a Biomarker of a Poor Prognosis in Invasive Breast Cancer and CHEK1 Inhibitor Efficacy in Breast Cancer Cells. Clin Cancer Res 24:1629-1643
Ozawa, Patricia Midori Murobushi; Alkhilaiwi, Faris; Cavalli, Iglenir João et al. (2018) Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells. Breast Cancer Res Treat 172:713-723
Ngankeu, Apollinaire; Ranganathan, Parvathi; Havelange, Violaine et al. (2018) Discovery and functional implications of a miR-29b-1/miR-29a cluster polymorphism in acute myeloid leukemia. Oncotarget 9:4354-4365
Lopez, Cecilia M; Yu, Peter Y; Zhang, Xiaoli et al. (2018) MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines. PLoS One 13:e0190086
Victor, Aaron R; Weigel, Christoph; Scoville, Steven D et al. (2018) Epigenetic and Posttranscriptional Regulation of CD16 Expression during Human NK Cell Development. J Immunol 200:565-572
Lampis, Andrea; Carotenuto, Pietro; Vlachogiannis, Georgios et al. (2018) MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. Gastroenterology 154:1066-1079.e5
Le Gallo, Matthieu; Rudd, Meghan L; Urick, Mary Ellen et al. (2018) The FOXA2 transcription factor is frequently somatically mutated in uterine carcinosarcomas and carcinomas. Cancer 124:65-73
Jones, Jeffrey A; Mato, Anthony R; Wierda, William G et al. (2018) Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol 19:65-75
Madan, Esha; Parker, Taylor M; Bauer, Matthias R et al. (2018) The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53. J Biol Chem 293:4262-4276

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