The Hormone Related Malignancies (HRM) Program members study cancers of the reproductive tract and breast, and research the role of hormones in establishing and maintaining these cancers, the progression of these cancers to hormone-independent states, and mechanisms contributing to metastasis. The goal is to prevent, diagnose, and treat these cancers more effectively. Members are engaged in translating their knowledge of these processes into biomarkers and therapeutic targets for cancer patients through clinical trials. Novel technologies and approaches developed by the program to address these areas include 1) animal models to study epithelial to mesenchymal transition (EMT), cancer stem cells, apoptosis, and the microenvironment's role in metastasis;and 2) functional genomic and high throughput screens to identify new drugs targeting novel pathways in HRM-related cancers. The HRM Program includes highly interactive basic researchers and clinicians that promote the translational nature of the research conducted. HRM has two focus groups: 1) Women's Cancers, and 2) Prostate Cancer. In the prior funding period HRM made several major contributions to the field including: 1) Demonstration that screening does not reduce 10-year prostate cancer mortality, shedding light on the controversy surrounding prostate cancer screening {New Eng J of Med);2) The identification of Six1 as a critical tumor and metastasis promoting factor (J Clin Invest), and development of a program to identify small molecules of the Six1/Eya complex as an anti-breast cancer strategy;3) Discovery that the pro-inflammatory involution microenvironment stimulates pregnancy-associated breast cancer, leading to a clinical trial of fish oil and celecoxib in women with newly diagnosed breast cancer;and 4) The contribution of new recommendations for using 5 alpha-reductase inhibitors for prostate cancer prevention based on pathological characteristics observed in tumors of the Prostate Cancer Prevention Trial (New Eng J of Med, J Natl Cancer Inst, and Cancer Prev Res). HRM has 29 full members in 9 Departments and 3 schools at UCD and Colorado State University (CSU). HRM researchers currently hold $3.8M direct costs in NCI grants and $7.4M direct costs in other cancer relevant grants. Since 2005, per capita cancer research funding has increased by 56% from $247K to $385K. HRM produced 435 cancer-related publications from 2005-2010. Of these, 115 (26%) were interprogrammatic; 63 (15%) were intra-programmatic;and 52 (12%) were both inter- and intra-programmatic. Thus, 230 (53%) of the total cancer-related publications by members of this program were collaborative.

Public Health Relevance

The Hormone Related Malignancies Program (HRM) fosters cancer-focused inter-disciplinary research among basic scientists, clinical researchers and epidemiologists who study cancers of the reproductive tract and breast The goal is to prevent, diagnose, and treat these cancers more effectively through the translation of lab-based discoveries into therapeutic targets.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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University of Colorado Denver
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Harder, Bryan; Tian, Wang; La Clair, James J et al. (2017) Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog 56:1493-1500
Chen, Yufei; Anastassiadis, Konstantinos; Kranz, Andrea et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31:755-770.e6
DeRyckere, Deborah; Lee-Sherick, Alisa B; Huey, Madeline G et al. (2017) UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models. Clin Cancer Res 23:1481-1492
Scarborough, Hannah A; Helfrich, Barbara A; Casás-Selves, Matias et al. (2017) AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. Clin Cancer Res 23:1531-1541
Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773
Barón, Anna E; Kako, Severine; Feser, William J et al. (2017) Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. J Thorac Oncol 12:1512-1523
Todd, Maria C; Langan, Thomas A; Sclafani, Robert A (2017) Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. J Cancer 8:190-198
Brown, Dustin G; Borresen, Erica C; Brown, Regina J et al. (2017) Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. Br J Nutr 117:1244-1256
Haverkos, Bradley M; Abbott, Diana; Hamadani, Mehdi et al. (2017) PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 130:221-228
Shearn, Colin T; Saba, Laura M; Roede, James R et al. (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radic Biol Med 113:280-290

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