Primary human xenografts are human cancer tissues which are xenotransplanted into immunodeficient mice. Numerous studies have demonstrated that these xenografts much more closely resemble primary human cancers at the histological and molecular level then do xenografts generated from cell lines propagated in vitro (f-3). Primary xenograft models have proven most valuable in studying tumor biology and cellular heterogeneity, as well as for evaluating the efficacy of therapeutic agents. A prime example of the utility of primary human xenografts has been In the identification and characterization of human cancer stem cells (CSCs). UMCCC investigators used these models to report the Initial identification of CSCs in cancers of the breast, pancreas, head and neck and ovaries (4-6). Subsequently, xenograft models have been utilized by other UMCCC investigators to investigate CSCs in the brain, liver, adrenal and lung cancers {9-11). In addition to identifying CSC populations In various tumor types, these models have proven invaluable in studying the pathways which regulate them and in developing CSC-based therapeutics. Indeed, agents targeting CSCs regulatory pathways including Notch, Hedgehog, HER2/Akt, Wnt and cytokine signaling are being evaluated In multiple tumor types by UMCCC investigators. These preclinical studies have already led to the development of several early stage clinical trials targeting these CSC pathways. An important component of the translational oncology research strategy involves the development and testing of molecular targeted therapeutics In these xenograft models.

Public Health Relevance

The Primary Tumor Xenograft Core will establish individual patient tumors in mice to allow the study of individual patient tumors lo best design personalized therapeutics. A broad range of tumors will be analyzed.

Agency
National Institute of Health (NIH)
Type
Center Core Grants (P30)
Project #
5P30CA046592-26
Application #
8696622
Study Section
Subcommittee B - Comprehensiveness (NCI)
Project Start
Project End
Budget Start
Budget End
Support Year
26
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Ro, Seung-Hyun; Semple, Ian A; Park, Haewon et al. (2014) Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. FEBS J 281:3816-27
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