Our recent discovery of conditional reprogramming (CR) to generate cell cultures from human tissues offers new and exciting opportunities for biospecimen repositories. This cell technology makes it possible to rapidly generate cell cultures from surgical specimens and small biopsies, thereby providing an unlimited amount of patient material for genetic and proteomic analysis. However, this technology goes further: it will allow the functional analysis of tumor cells and comparison with the patients'normal cells from the same tissue. In this proposal we will extend and validate aspects of the CR technology and optimize its usage for biobanking. It is important to verify that the genotype and functional responses of CR cells mimics that of the primary tumor and experiments will address these issues using exome sequencing and TruSeq analysis. We will also examine whether the CR cells can predict patient responses to therapies, as we have recently described for a single case in the New England Journal of Medicine. Indeed, we believe that this technology will alter how Pathology departments and tissue repositories freeze patient specimens. Rather than simply quick freezing samples for future molecular analysis, tumor samples will be frozen in cryopreservative, which will additionally permit the generation of cell cultures for diagnostic and therapeutic evaluation.

Public Health Relevance

Earlier this year we published as study showing that it is now possible to establish cell cultures from normal and tumor tissue of cancer patients and to expand them rapidly and efficiently so that they can be used for diagnostic and therapeutic purposes. The intent of this proposal is to optimize and standardize this system so that it can be used by many medical centers for storing and studying a patient's tumor. This method not only provides unlimited material for oncologists to study, but it represents a potential new approach for truly personalized medicine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
1R33CA177466-01
Application #
8547303
Study Section
Special Emphasis Panel (ZCA1-SRLB-5 (M1))
Program Officer
Ossandon, Miguel
Project Start
2013-09-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$400,506
Indirect Cost
$140,498
Name
Georgetown University
Department
Pathology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Yuan, Hang; Krawczyk, Ewa; Blancato, Jan et al. (2017) HPV positive neuroendocrine cervical cancer cells are dependent on Myc but not E6/E7 viral oncogenes. Sci Rep 7:45617
Timofeeva, Olga A; Palechor-Ceron, Nancy; Li, Guanglei et al. (2017) Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer. Oncotarget 8:22741-22758
Berens, E B; Sharif, G M; Schmidt, M O et al. (2017) Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion. Oncogene 36:593-605
Vietsch, Eveline E; Graham, Garrett T; McCutcheon, Justine N et al. (2017) Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer. Cancer Genet 218-219:39-50
Dakic, Aleksandra; DiVito, Kyle; Fang, Shuang et al. (2016) ROCK inhibitor reduces Myc-induced apoptosis and mediates immortalization of human keratinocytes. Oncotarget 7:66740-66753
Berens, Eric B; Sharif, Ghada M; Wellstein, Anton et al. (2016) Testing the Vascular Invasive Ability of Cancer Cells in Zebrafish (Danio Rerio). J Vis Exp :
Sharif, G M; Schmidt, M O; Yi, C et al. (2015) Cell growth density modulates cancer cell vascular invasion via Hippo pathway activity and CXCR2 signaling. Oncogene 34:5879-89
Sharif, Ghada M; Wellstein, Anton (2015) Cell density regulates cancer metastasis via the Hippo pathway. Future Oncol 11:3253-60
Vietsch, Eveline E; van Eijck, Casper Hj; Wellstein, Anton (2015) Circulating DNA and Micro-RNA in Patients with Pancreatic Cancer. Pancreat Disord Ther 5:
Saenz, Francisco R; Ory, Virginie; AlOtaiby, Maram et al. (2014) Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype. PLoS One 9:e97666

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