Ovarian cancer has the highest mortality rate of the "women's cancers" (breast and gynecologic cancers). The Mayo Clinic SPORE in Ovarian Cancer features a team of basic, clinical, and population science Investigators conducting translational research designed to reduce the burden of ovarian cancer. The translational science of this SPORE includes four projects. Project 1, "Poisoning of PARP and topoisomerase I to treat ovarian cancer," studies the effect of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-888 alone and In combination with topotecan. In addition to elucidating how ABT-888 converts PARP Into an enzyme that actively contributes to the demise of topotecan-treated ovarian cancer cells, this project will examine a series of tumor markers for their ability to predict response in a topotecan/ABT-888 phase II trial. Project 2, "Mechanisms of immunosuppression in ovarian cancer," our population sciences project, studies the components of microenvironmental immunosuppression in ovarian cancer. Based in a large cohort of ovarian cancer cases, the work will examine differences in inherited variation in regulatory T-cell-related genes, the quantity of Tregs In the microenvironment and outcome after diagnosis. Project 3. "Optimizing measles virotherapy in the treatment of recurrent ovarian cancer," builds upon our in vitro and phase I clinical trial data showing promising anti-tumor activity with the attenuated vaccine strain of measles virus delivered intraperitoneally in women with recurrent ovarian cancer. In this project we will study the possibility of systemic administration of the virus and measures to enhance cytotoxicity of the virus. Project 4. "Flavopiridol reverses platinum resistance in ovarian cancer," builds upon work at Mayo showing that flavopiridol combines with cisplatin to yield cytotoxic synergy. We completed a phase I trial of this combination and now in a phase II trial in platinum-resistant ovarian cancer, have observed a 33% response rate, which is twice the mean response rate typically seen in this setting. This project will study the mechanism of synergy and attempt to improve upon the combination by adding a third agent and/or identifying predictive biomarkers in tumor samples from responders vs. non-responders. Four cores (Administration, Biospecimens/Patient Registry, Animal Models, and Biostatistics) provide the infrastructure support for the translational research of the SPORE. A Developmental Research Program has been established to foster promising research initiatives;and a Career Development Program will promote the research careers of junior or more established investigators who wish to pursue ovarian cancer translational research. The Mayo Clinic SPORE in Ovarian Cancer has the full support of the Mayo Clinic Cancer Center and Mayo Foundation.

Public Health Relevance

Of the women's cancers (breast and gynecologic cancers), ovarian cancer has the highest mortality rate. In this SPORE application, we explore one important pathogenic process -- immunosuppression -- that underlies ovarian cancer and three novel, promising treatment approaches for this disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA136393-05
Application #
8547763
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (M1))
Program Officer
Arnold, Julia T
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$2,150,500
Indirect Cost
$756,858
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Karami, Sara; Han, Younghun; Pande, Mala et al. (2016) Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer 139:2655-2670
Radecki Breitkopf, Carmen; Ridgeway, Jennifer L; Asiedu, Gladys B et al. (2016) Ovarian cancer patients' and their family members' perspectives on novel vaccine and virotherapy trials. Clin Trials 13:660-664
Clyde, Merlise A; Palmieri Weber, Rachel; Iversen, Edwin S et al. (2016) Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci. Am J Epidemiol 184:579-589
Li, Zheng; Block, Matthew S; Vierkant, Robert A et al. (2016) The inflammatory microenvironment in epithelial ovarian cancer: a role for TLR4 and MyD88 and related proteins. Tumour Biol 37:13279-13286
Ezewuiro, Obiageli; Grushko, Tatyana A; Kocherginsky, Masha et al. (2016) Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy. PLoS One 11:e0147145
(2016) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus. Nat Commun 7:12675
Pharoah, Paul D P; Song, Honglin; Dicks, Ed et al. (2016) PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations. J Natl Cancer Inst 108:
French, Juliet D; Johnatty, Sharon E; Lu, Yi et al. (2016) Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer. Oncotarget 7:6353-68
Karyampudi, Lavakumar; Lamichhane, Purushottam; Krempski, James et al. (2016) PD-1 Blunts the Function of Ovarian Tumor-Infiltrating Dendritic Cells by Inactivating NF-κB. Cancer Res 76:239-50
Harris, Faye R; Kovtun, Irina V; Smadbeck, James et al. (2016) Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-Free DNA from Ovarian Cancers. Sci Rep 6:29831

Showing the most recent 10 out of 225 publications