The theme of the Imaging Core is molecular imaging of mouse models of human breast cancer. The Core provides individual projects with non-invasive, quantitative imaging-based capabilities for metabolic and genetic characterization of tumors and their microenvironment, including in vivo trafficking of tumor cells. This will be accomplished by monitoring of """"""""directly-targeting"""""""" probes and of the expression of single and multi-modality reporter genes using optical (bioluminescence and fluorescence), radionuclide (PET, SPECT, and autoradiography), MRI/MRS, CT, and US) imaging. These quantitative, non-invasive imaging techniques are well-established at MSKCC for both smallanimal and patient imaging studies. They are quantitative and non-invasive and thus readily adaptable to longitudinal studies. The Imaging Core can readily provide [18F]-FDG, [18F]-FLT, [18F]-ACBC , and [I8F]-FMISO or [124I]-IAZG microPET to all RPs for non-invasive assessment of tumor glycolysis, cell proliferation, amino transport, and hypoxia, respectively, in mouse models of breast cancer. Further, a number of inducible reporter systems for non-invasive in vivo imaging in small animals have been developed. These reporter systems are all multi-modality reporters and include the capability for fluorescence, bioluminescence and radionuclide imaging. In addition to p53 and DFHR, the list of inducible reporters includes NFAT, FIRE (hypoxia response element - hypoxia inducible factor), E2F, Forkhead factor (FOXO), heat shock protein 70 (HSP70) and TGFp. A general two-step strategy is generally pursued in probe development: first, to establish and validate imaging and non-invasive assay techniques in experimental animals, and second, to translate where appropriate selected aspects of our imaging technology to patient studies within the context of the Research Projects (RPs) proposed in this Application. The Imaging Core will actively and directly support all five RPs, led by Harold Varmus, Joan Massague, Neil Rosen, Maria Jasin, and Robert Benezra, respectively.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA094060-09
Application #
8323081
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
9
Fiscal Year
2011
Total Cost
$325,805
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Er, Ekrem Emrah; Valiente, Manuel; Ganesh, Karuna et al. (2018) Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol 20:966-978
Chen, Chun-Chin; Kass, Elizabeth M; Yen, Wei-Feng et al. (2017) ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair. Proc Natl Acad Sci U S A 114:7665-7670
Kass, Elizabeth M; Lim, Pei Xin; Helgadottir, Hildur R et al. (2016) Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation. Nat Commun 7:13241
She, Qing-Bai; Gruvberger-Saal, Sofia K; Maurer, Matthew et al. (2016) Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer. BMC Cancer 16:587
Yang, C; Li, Z; Bhatt, T et al. (2016) Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene :
Gao, Hua; Chakraborty, Goutam; Zhang, Zhanguo et al. (2016) Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling. Cell 166:47-62
Ebbesen, Saya H; Scaltriti, Maurizio; Bialucha, Carl U et al. (2016) Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas. Proc Natl Acad Sci U S A 113:3030-5
Malladi, Srinivas; Macalinao, Danilo G; Jin, Xin et al. (2016) Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT. Cell 165:45-60
Rodrik-Outmezguine, Vanessa S; Okaniwa, Masanori; Yao, Zhan et al. (2016) Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature 534:272-6
Chen, Qing; Boire, Adrienne; Jin, Xin et al. (2016) Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533:493-498

Showing the most recent 10 out of 97 publications