This proposal represents the second competing renewal of Vanderbilt's GI SPORE. This SPORE continues to focus on colorectal cancer, the second leading cause of cancer deaths in the US, where it affects more men and women than all other gastrointestinal malignancies combined. Over the last four years, Vanderbilt's GI SPORE has made discoveries and advances that hold great promise toward improvement of the management of individuals with colorectal neoplasia. These include 1) discovery of a novel Wnt antagonist (pyrvinium) and its target (casein kinase 1alpha ) , 2) discovery of a biologically-based, prognostic gene signature for colorectal cancer, 3) evidence that p120 acts as a tumor suppressor in colorectal cancer, 4) development, biological validation and clinical implementation of novel molecular imaging modalities to predict early response to treatment and 5) further development of a unique biorepository of colorectal adenomas, as well as matched normal rectal mucosa and bodily fluids (serum and urine). Our potential for continued success is high based on 1) productivity during the past funding cycles, 2) strong and highly integrative institutional support, 3) recruitment of talented investigators to the field of GI cancer through career development and pilot project funding, 4) access to unparalleled resources for proteomics, drug discovery and small animal imaging, 5) a team of highly interactive clinical investigators and basic scientists working together in a collegial environment and 6) strong Inter-SPORE, pharmaceutical, national and international collaborations. After a rigorous internal and external review process followed by consultation with NCI SPORE administrators, we propose three new projects and continuation of one project. Project 1. Multimodal Imaging &Targeted Therapeutics of Stem Cell-Derived Colon Cancer Project 2. Targeting K-RAS in Colorectal Cancer Project 3. Molecular Markers of Colorectal Cancer Recurrence Project 4. Genetic &Epigenetic Markers of Colorectal Adenoma Recurrence Core A. Administrative Core B. Translational Pathology &Imaging Core C. Biostatistics &Bioinformatics Career Development Program Developmental Research Program

Public Health Relevance

These four projects will transform how we diagnose and treat individuals with colorectal cancer and deepen our understanding of the pathobiology of colorectal neoplasia. A patient advocate is an integral member of each project to help ensure that our translational goals are being met.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA095103-11
Application #
8335621
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (M1))
Program Officer
Agarwal, Rajeev K
Project Start
1997-02-28
Project End
2017-04-30
Budget Start
2012-09-07
Budget End
2013-04-30
Support Year
11
Fiscal Year
2012
Total Cost
$2,300,000
Indirect Cost
$824,300
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Jin, Ming; Roth, Rachel; Rock, Jonathan B et al. (2015) The impact of tumor deposits on colonic adenocarcinoma AJCC TNM staging and outcome. Am J Surg Pathol 39:109-15
Johnson, Adam; Wright, Jesse P; Zhao, Zhiguo et al. (2015) Cadherin 17 is frequently expressed by 'sclerosing variant' pancreatic neuroendocrine tumour. Histopathology 66:225-33
Peng, DunFa; Hu, TianLing; Soutto, Mohammed et al. (2014) Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma. Gut 63:540-51
Tripathi, Manish K; Deane, Natasha G; Zhu, Jing et al. (2014) Nuclear factor of activated T-cell activity is associated with metastatic capacity in colon cancer. Cancer Res 74:6947-57
Powell, Anne E; Vlacich, Gregory; Zhao, Zhen-Yang et al. (2014) Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. Am J Physiol Gastrointest Liver Physiol 307:G16-23
Hight, Matthew R; Cheung, Yiu-Yin; Nickels, Michael L et al. (2014) A peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells. Clin Cancer Res 20:2126-35
Zhang, Bing; Wang, Jing; Wang, Xiaojing et al. (2014) Proteogenomic characterization of human colon and rectal cancer. Nature 513:382-7
Mitra, Ramkrishna; Edmonds, Mick D; Sun, Jingchun et al. (2014) Reproducible combinatorial regulatory networks elucidate novel oncogenic microRNAs in non-small cell lung cancer. RNA 20:1356-68
Sekhar, Konjeti R; Benamar, Mouadh; Venkateswaran, Amudhan et al. (2014) Targeting nucleophosmin 1 represents a rational strategy for radiation sensitization. Int J Radiat Oncol Biol Phys 89:1106-14
Sehdev, Vikas; Katsha, Ahmed; Arras, Janet et al. (2014) HDM2 regulation by AURKA promotes cell survival in gastric cancer. Clin Cancer Res 20:76-86

Showing the most recent 10 out of 239 publications