The mission of the Molecular Oncology Program (MO) is to integrate and coordinate research with a focus on identifying and exploring anti-cancer targets, particularly those that distinguish cancer from noncancer cells based on growth, differentiation and survival. Key accomplishments in this Program include the discovery of a novel small molecule that targets an oncogenic fusion protein, STAG2 as a regulator of chromosomal integrity that is deleted in many cancers, and a novel method to chemically reprogram cancer cells. Continued emphasis is on discovering small molecule probes that may lead to future novel therapeutics and biomarkers. To accomplish this mission, MO members perform research around three themes: Theme 1 focuses on unique genomic events that initiate and sustain cancer growth: mechanisms deregulating chromosomal integrity and the role of oncogenic chromosomal translocations in malignancy. Theme 2 focuses on the immortal lives of cancer cells: studies on cellular immortalization;cancer prevention by dietary components that modulate DNA repair mechanisms;and the effect of nutrients on the activity of mutant p53 and its role in transcriptional activation in DNA repair. Theme 3 focuses on the metastatic mechanisms that allow the spread of cancer: discovering novel regulators of metastatic pathways and identifying useful small molecule inhibitors. Led by Jeffrey Toretsky, MD, and Vicente Notario, PhD, the Program has 17 members and includes faculty from six Georgetown University departments. Total peer review funding is $5.9M (direct) in the last budget year, of which $4M is from NCI. MO members published 210 peer-reviewed publications, of which 35% involved external collaborations and 41% were intra- and/or interprogrammatic, the latter involving collaborations with all three other LCCC Programs. Research on small molecules targeting EWS-FLH and the conditionally reprogrammed cells methodology begun in MO have transitioned to the Experimental Therapeutics or Breast Cancer Programs for clinical trials. Members used all nine Shared Resources;MO research on cell immortalization was developed into a new shared service by the Center. The Cancer Center has added value to the Program through $16M in institutional support over the past funding period facilitating the recruitment and support of two new junior faculty members, by facilitating access to new technologies both within the Cancer Center or through external affiliations with other institutions.

Public Health Relevance

): While the Program is neither disease-specific nor therapy-focused, it develops the basic scientific underpinnings for prevention and targeted therapies across all cancer types. For example, prostate cancer and the human papilloma virus (HPV) are major areas of emphasis investigated by MO researchers that have important regional implications due to the high rate of prostate cancer and HPV infection in our catchment area.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA051008-21
Application #
8698913
Study Section
Subcommittee G - Education (NCI)
Project Start
1997-08-15
Project End
2019-04-30
Budget Start
2014-09-09
Budget End
2015-04-30
Support Year
21
Fiscal Year
2014
Total Cost
$38,982
Indirect Cost
$13,913
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Lee, Yichien; Rodriguez, Olga C; Albanese, Chris et al. (2018) Divergent brain changes in two audiogenic rat strains: A voxel-based morphometry and diffusion tensor imaging comparison of the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR). Neurobiol Dis 111:80-90
Coia, Heidi; Ma, Ning; Hou, Yanqi et al. (2018) Prevention of Lipid Peroxidation-derived Cyclic DNA Adduct and Mutation in High-Fat Diet-induced Hepatocarcinogenesis by Theaphenon E. Cancer Prev Res (Phila) 11:665-676
Ory, Virginie; Kietzman, William B; Boeckelman, Jacob et al. (2018) The PPAR? agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ. Breast Cancer Res Treat 169:47-57
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
Smith, Jill P; Wang, Shangzi; Nadella, Sandeep et al. (2018) Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and increases efficacy of immune checkpoint antibody therapy in mice. Cancer Immunol Immunother 67:195-207
Edwardson, Matthew A; Zhong, Xiaogang; Fiandaca, Massimo S et al. (2018) Plasma microRNA markers of upper limb recovery following human stroke. Sci Rep 8:12558
Kaat, Aaron J; Schalet, Benjamin D; Rutsohn, Joshua et al. (2018) Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT). Cancer 124:153-160
Maximov, Philipp Y; Abderrahman, Balkees; Fanning, Sean W et al. (2018) Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer. Mol Pharmacol 94:812-822
Czarnecka, Magdalena; Lu, Congyi; Pons, Jennifer et al. (2018) Neuropeptide Y receptor interactions regulate its mitogenic activity. Neuropeptides :
Gonzalez, Thomas L; Moos, Rebecca K; Gersch, Christina L et al. (2018) Metabolites of n-Butylparaben and iso-Butylparaben Exhibit Estrogenic Properties in MCF-7 and T47D Human Breast Cancer Cell Lines. Toxicol Sci 164:50-59

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