Medulloblastoma (MB) is the most common malignant brain tumor in children. Its rapid growth and tendency to spread through the nervous system necessitate the use of extreme aggressive and toxic therapies. Even with such therapies, a significant proportion of patients die from this disease, and survivors often suffer severe long-term side effects such as cognitive deficits and endocrine disorders. Improved strategies for treating MB are urgently needed. The goal of this study is to explore the targeted therapeutic approaches for MB. Preliminary studies suggest that a cytoskeletal protein, Nestin is essential for MB cell proliferation. In this proposal, investigators will further determine the mechanisms for Nestin in promoting MB development. In addition, recent studies have revealed that leukotriene, a lipid mediator, is required for Nestin expression in tumor cells and inhibitionof leukotriene synthesis significantly prevents tumor cell proliferation. This study therefore proposes to examine the therapeutic potentials of leukotriene inhibitors in treating MBs in mice. These studies would significantly deepen our understanding of the molecular basis for MB development, and pave the road for the application of leukotriene inhibitors in treating human MB.

Public Health Relevance

Identifying the critical role of Nestin in medulloblastoma development will contribute to our understanding of the molecular basis for this disease. Moreover, demonstration of the requirement of leukotriene for Nestin expression and tumor progression will facilitate the potential therapeutic application of leukotriene inhibitors for treting human medulloblastoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA178380-05
Application #
9392899
Study Section
Molecular Oncogenesis Study Section (MONC)
Program Officer
Espey, Michael G
Project Start
2014-01-01
Project End
2018-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Research Institute of Fox Chase Cancer Center
Department
Type
DUNS #
064367329
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
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Gordon, Renata E; Zhang, Li; Yang, Zeng-Jie (2017) Restore the brake on tumor progression. Biochem Pharmacol 138:1-6
Li, Peng; Lee, Eric H; Du, Fang et al. (2016) Nestin Mediates Hedgehog Pathway Tumorigenesis. Cancer Res 76:5573-83
Yuelling, Larra W; Du, Fang; Li, Peng et al. (2014) Isolation of distinct cell populations from the developing cerebellum by microdissection. J Vis Exp :52034
Li, Peng; Du, Fang; Yuelling, Larra W et al. (2013) A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity. Nat Neurosci 16:1737-44