This Specialized Program of Research Excellence (SPORE) in Endometrial Cancer is submitted by Washington University in St. Louis, the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. It includes four research projects, three supportive cores, and research and career development programs. This proposal brings together basic and applied investigators to conduct innovative and diverse translational investigations aimed at preventing, diagnosing and treating endometrial cancer. The four projects in our application have been carefully designed to have significant potential to change clinical practice within five years. Project 1: FGFR2 as therapeutic target in endometrial cancer Project 2: Methylation markers for prognosis in endometrioid endometrial cancers Project 3: Identifying inherited endometrial cancer &the environmental and genetic factors contributing to somatic loss of mismatch repair Project 4: Novel effectors of ERK signaling and their potential roles in the treatment of endometrial cancer The four projects represent carefully chosen marriages between selected endometrial cancer research priorities and the strengths of Washington University and our collaborators. The critical objectives that we have chosen to focus on are to: 1) improve the treatment of patients with persistent or recurrent endometrial cancer using a molecularly targeted therapy and determine if upfront adjuvant biologic therapies hold promise for improving outcomes in the general endometrial cancer population;2) develop prognostic markers to help guide the treatment of women with the most common form of uterine tumors, endometrioid endometrial cancer;3) optimize detection of those women with inherited forms of endometrial cancer so they and their at-risk family members can receive risk-appropriate (intensified) cancer surveillance;and 4) elucidate the role novel effectors of ERK signaling play in uterine cancer and assess opportunities for targeting these in the treatment of endometrial cancers. Three Cores will support these projects: Administration, Tissue &Pathology, and Biostatistics. The Developmental Research Program will support a pathway for continued identification and support of diverse research that could replace or improve current projects, and a Career Development Program will recruit and support candidates committed to training in translational research in endometrial cancer.

Public Health Relevance

The work proposed will lead to both an improved understanding of endometrial cancer biology and new approaches to the detection, prevention and treatment of uterine cancers which will result in reduced cancer morbidity and mortality.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA134254-03
Application #
8119020
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (M1))
Program Officer
Kuzmin, Igor A
Project Start
2009-09-18
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$475,000
Indirect Cost
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Li, Jing; Xing, Xiaoyun; Li, Daofeng et al. (2017) Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma. Neoplasia 19:100-111
Jeske, Yvette W; Ali, Shamshad; Byron, Sara A et al. (2017) FGFR2 mutations are associated with poor outcomes in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 145:366-373
Rocconi, Rodney P; Lankes, Heather A; Brady, William E et al. (2016) The role of racial genetic admixture with endometrial cancer outcomes: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 140:264-9
McMeekin, D Scott; Tritchler, David L; Cohn, David E et al. (2016) Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol 34:3062-8
Goodfellow, Paul J; Billingsley, Caroline C; Lankes, Heather A et al. (2015) Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol 33:4301-8
Frolova, Antonina I; Babb, Sheri A; Zantow, Emily et al. (2015) Impact of an immunohistochemistry-based universal screening protocol for Lynch syndrome in endometrial cancer on genetic counseling and testing. Gynecol Oncol 137:7-13
Huang, Yi-Wen; Kuo, Chieh-Ti; Chen, Jo-Hsin et al. (2014) Hypermethylation of miR-203 in endometrial carcinomas. Gynecol Oncol 133:340-5
Wang, Li-Shu; Burke, Carol A; Hasson, Henrietta et al. (2014) A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis. Cancer Prev Res (Phila) 7:666-74
Powell, Matthew A; Sill, Michael W; Goodfellow, Paul J et al. (2014) A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 135:38-43
Nagarajan, Raman P; Zhang, Bo; Bell, Robert J A et al. (2014) Recurrent epimutations activate gene body promoters in primary glioblastoma. Genome Res 24:761-74

Showing the most recent 10 out of 33 publications