Through this application, The University of Texas MD Anderson Cancer Center seeks funding for renewal of its Prostate Cancer SPORE. This application is submitted under the Multiple Principal Investigator plan (MPI) by Principal Investigators Drs. Christopher J. Logothetis and Timothy C. Thompson, who are recognized internationally for their research in prostate cancer, The MD Anderson Prostate Cancer SPORE has created a stable and dynamic infrastructure for translational research to meet and successfully address specific challenges in reducing suffering and mortality rates for men with prostate cancer. We continue to build on our capacity to conduct novel, innovative clinical trials and believe that new research projects conducted by our translational research team will yield substantial progress and meaningful changes in clinical practice. In the current proposal, we define our translational research challenges and goals as (1) quantitative definition of prostate cancer risk to eliminate overtreatment of low-risk prostate cancer, (2) development of novel therapeutic approaches to overcoming resistance of castration-resistant prostate cancer (CRPC) to available therapies, and (3) development of novel alternative strategies for CRPC and treatment-refractory disease. We will achieve these translational research goals by identifying and testing novel predictive and prognostic biomarkers to determine the need for therapy in patients with early-stage prostate cancer, developing and testing novel immunotherapy for CRPC, developing and testing a novel approach to overcoming osteocrine- mediated resistance of bone metastasis to therapy, and developing and testing lead-in combination therapy to maximize DNA damage response-targeted therapy for CRPC. We will accomplish our goals via 4 research projects (including one population science research project), 3 support cores (Administrative, Biostatistics and Bioinformatics, and Biospecimen and Pathology), a dynamic Developmental Research Program, and an effective Career Enhancement Program. We are optimistic that our research efforts will contribute to reductions in the incidence, morbidity, and mortality of this devastating disease by translating basic research findings into clinical practice.

Public Health Relevance

Despite substantive strides in detecting and treating prostate cancer, this disease continues to take an unacceptable toll on the lives of tens of thousands of men in the United States. The MD Anderson Cancer Center Prostate Cancer SPORE will address the critical gaps in our understanding and treatment of this devastating disease by (1) developing predictive tools to better inform prostate cancer patients with low-risk disease to make evidence-based decisions and thereby eliminate overtreatment; (2) developing a clear understanding of the molecular mechanisms of resistance to currently available, diverse therapies for castrate- resistant prostate cancer (CRPC), including 2nd generation inhibitors of androgen signaling, immunotherapy, chemotherapy, and bone-homing radiopharmaceuticals and developing combination therapies to overcome these resistance mechanisms; and (3) developing novel therapeutic options for men with CRPC and treatment-refractory prostate cancer. Our laboratory and clinical studies build on the vast experience, expertise, and infrastructure of MD Anderson Prostate Cancer SPORE investigators.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA140388-06A1
Application #
8999522
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Hruszkewycz, Andrew M
Project Start
2009-09-02
Project End
2021-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Dentistry
Type
Hospitals
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Luo, Yong; Azad, Abul Kalam; Karanika, Styliani et al. (2017) Enzalutamide and CXCR7 inhibitor Combination Treatment Suppresses Cell Growth and Angiogenic Signaling in Castration-Resistant Prostate Cancer Models. Int J Cancer :
Lin, Song-Chang; Lee, Yu-Chen; Yu, Guoyu et al. (2017) Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. Dev Cell 41:467-480.e3
Gao, Jianjun; Ward, John F; Pettaway, Curtis A et al. (2017) VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med 23:551-555
Yu, Kai-Jie; Li, Jeffrey K; Lee, Yu-Chen et al. (2017) Cabozantinib-induced osteoblast secretome promotes survival and migration of metastatic prostate cancer cells in bone. Oncotarget 8:74987-75006
Tu, Huakang; Gu, Jian; Meng, Qing H et al. (2017) Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer. Oncol Lett 13:1949-1957
Gökce, Mehmet I; Wang, Xuemei; Frost, Jacqueline et al. (2017) Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men. Cancer 123:583-591
Karanika, Styliani; Karantanos, Theodoros; Li, Likun et al. (2017) Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling. Cell Rep 18:1970-1981
Saha, Achinto; Blando, Jorge; Fernandez, Irina et al. (2016) Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo. Oncotarget 7:25194-207
Fong, Eliza L S; Wan, Xinhai; Yang, Jun et al. (2016) A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. Biomaterials 77:164-72
Subudhi, Sumit K; Aparicio, Ana; Gao, Jianjun et al. (2016) Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities. Proc Natl Acad Sci U S A 113:11919-11924

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