@article{c78fe16114954d45ab0d42a1c5ee46c3,
title = "Quiescent Sox2+ Cells Drive Hierarchical Growth and Relapse in Sonic Hedgehog Subgroup Medulloblastoma",
abstract = "Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2+ cells propagate sonic hedgehog subgroup medulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox2+ cells produce rapidly cycling doublecortin+ progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox2+ cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox2+ cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox2+ cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox2+ cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.",
author = "Vanner, \{Robert J.\} and Marc Remke and Marco Gallo and Selvadurai, \{Hayden J.\} and Fiona Coutinho and Lilian Lee and Michelle Kushida and Renee Head and Sorana Morrissy and Xueming Zhu and Tzvi Aviv and Veronique Voisin and Clarke, \{Ian D.\} and Yisu Li and Mungall, \{Andrew J.\} and Moore, \{Richard A.\} and Yussanne Ma and Jones, \{Steven J.M.\} and Marra, \{Marco A.\} and David Malkin and Northcott, \{Paul A.\} and Marcel Kool and Pfister, \{Stefan M.\} and Gary Bader and Konrad Hochedlinger and Andrey Korshunov and Taylor, \{Michael D.\} and Dirks, \{Peter B.\}",
note = "Funding Information: P.D. and M.T. hold Garron Family Research Chairs in Childhood Cancer Research and are supported by grants from the Canadian Institutes of Health Research (CIHR), the Ontario Institute for Cancer Research with funds from the Government of Ontario, and Genome Canada. P.D. also receives funding from the Canadian Cancer Society, the Hospital for Sick Children Foundation, Jessica{\textquoteright}s Footprint Foundation, the Hopeful Minds Foundation, and B.R.A.I.N. Child. M.T.{\textquoteright}s lab is also supported by Genome BC, the Terry Fox Research Institute, the Pediatric Oncology Group Ontario, funds from the family of Kathleen Lorette and the Clark H. Smith Brain Tumour Centre, the Montreal Children{\textquoteright}s Hospital Foundation and the Hospital for Sick Children Sonia and Arthur Labatt Brain Tumour Research Centre, the Chief of Research Fund, the Cancer Genetics Program, and B.R.A.I.N. Child. K.H. is supported by an NIH grant (5R01DK096034-02). R.V. is funded by a CIHR Vanier Canada graduate scholarship. We would like to thank the Sickkids-UHN Flow Cytometry Facility and Sickkids Imaging Facility for contributions to this work. ",
year = "2014",
month = jul,
day = "14",
doi = "10.1016/j.ccr.2014.05.005",
language = "English",
volume = "26",
pages = "33--47",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}