Noninvasive, longitudinal imaging of PDAC development, maintenance and therapeutic efficacy is a fundamental aspect for all portions of this P01. The core serves two specific purposes: a) as a high-tech core and intellectual resource to perform and assist with all In vivo Imaging experiments and b) as an Innovative research core to develop new Imaging protocols and agents for high priority targets derived from different projects. The Projects will use the Core not only to detect the location and size of tumors, but importantly also to monitor responses to drugs that target specific pathways. For example, activation of the K-Ras and PI3K pathways turns on genes for glucose uptake and metabolism;drugs that turn off these pathways often cause acute changes in 18FDG-PET, prior to tumor shrinkage. Likewise, Myc regulates genes for glucose uptake so drugs that affect the Myc pathway are also expected to have acute effects on glucose uptake and metabolism. The Core efficiently leverages existing imaging resources but focuses specifically on unique aspects of PDAC biology and therapeutic interventions proposed in the Projects. Specifically the core will provide: a) all routine imaging technologies and protocols for PDAC imaging in GEMS, b) techniques and imaging protocols that are clinically translatable including MRI and PET-CT, c) high throughput optical screening capabilities, d) technical expertise for quantitative image analysis, e) the necessary infrastructure and expertise for image archival and distribution throughout the consortium, f) expertise in the design, synthesis and validation of novel imaging probes relevant to the goals of the projects and g) physiologic support and logistics for longitudinal Imaging in cohorts of mice including housing. The core is supported by a substantial infrastructure in the Center for Systems Biology at MGH, which includes a broad biological chemistry effort, computation and quantitative Image analysis, as well as a web-based bioinformatics platform (MlPortal) to assure access to imaging studies.

Public Health Relevance

The core will provide stability to the overall program and allow the investigators to focus on and efficiently address critical issues relevant to the goals of this P01. Centralization of the imaging efforts will also reduce overall mouse costs (by decreasing the number of mice needed in therapeutic studies), provide a higher level of expertise and promote interactions among the participating groups. Added benefits of this core are the high level of quality control, consistency of imaging protocols and reagents and efficient cross-reference of imaging results from different projects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA117969-09
Application #
8603771
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
Project End
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
9
Fiscal Year
2014
Total Cost
$198,008
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Biancur, Douglas E; Paulo, Joao A; Ma?achowska, Beata et al. (2017) Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism. Nat Commun 8:15965
Ravez, Séverine; Corbet, Cyril; Spillier, Quentin et al. (2017) ?-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH). J Med Chem 60:1591-1597
Nejati, Reza; Goldstein, Jennifer B; Halperin, Daniel M et al. (2017) Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy. Pancreas 46:1180-1187
Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu; Cancer Genome Atlas Research Network (2017) Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell 32:185-203.e13
Lu, Xin; Horner, James W; Paul, Erin et al. (2017) Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543:728-732
Lyssiotis, Costas A; Kimmelman, Alec C (2017) Metabolic Interactions in the Tumor Microenvironment. Trends Cell Biol 27:863-875
Pergolini, Ilaria; Morales-Oyarvide, Vicente; Mino-Kenudson, Mari et al. (2017) Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survival. PLoS One 12:e0182855
Sherman, Mara H; Yu, Ruth T; Tseng, Tiffany W et al. (2017) Stromal cues regulate the pancreatic cancer epigenome and metabolome. Proc Natl Acad Sci U S A 114:1129-1134
Shukla, Surendra K; Purohit, Vinee; Mehla, Kamiya et al. (2017) MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer. Cancer Cell 32:71-87.e7
Dey, Prasenjit; Baddour, Joelle; Muller, Florian et al. (2017) Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature 542:119-123

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