Brain tumors in humans have stem cells central to their biology and therapeutic response. Dr. Holland's laboratory has created histologically and genetically accurate mouse models of gliomas and medulloblastomas. These mouse models also replicate the resistant stem cells and their perivascular niche found in humans. They are studying the biology of therapeutic response in these stem cells relative to the bulk of the cells in the tumor. This system is more experimentally tractable than studying patient samples and the results are transferable to human brain tumors. Based on their data they are performing clinical trials in brain tumor patients here at MSKCC.
Hambardzumyan D, Squatrito M, Carbajal E, Holland EC. Glioma Formation, Cancer Stem Cells, and Akt Signaling. Stem Cell Rev. 2008 Jul 2. [Epub ahead of print]
Hambardzumyan D, Becher OJ, Holland EC. Cancer stem cells and survival pathways. Cell Cycle. 2008 May;7(10):1371-8. Epub 2008 Mar 19.
Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev. 2008 Feb 15;22(4):436-48.