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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,9,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Lower-grade gliomas are often characterized by mutations in metabolism-related genes isocitrate dehydrogenase 1 (\n                    <jats:italic>IDH1<\/jats:italic>\n                    ) and\n                    <jats:italic>IDH2<\/jats:italic>\n                    . Resection of these tumors is constrained by adjacent eloquent cortex, resulting in local failures. Studies showed that IDH mutant cells are sensitive to metabolic therapeutics, but these drugs are limited by systemic toxicities. We hypothesized that application of metabolism-altering therapeutics at the surgical margin would improve tumor control and minimize toxicity. We developed an intraoperative diagnostic assay to identify IDH mutations. We show that intratumoral administration of sustained release formulations of metabolism-altering compound prolongs survival in a mouse model of IDH mutant glioma. This genotype-based paradigm introduces a workflow in surgical oncology that can be extended to other tumors characterized by targetable molecular alterations.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1805751115","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T15:14:28Z","timestamp":1533568468000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Genotype-targeted local therapy of glioma"],"prefix":"10.1073","volume":"115","author":[{"given":"Ganesh M.","family":"Shankar","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameya R.","family":"Kirtane","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Stephen E. and Catherine Pappas Center for Neuro-Oncology, Division of Hematology\/Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hormoz","family":"Mazdiyasni","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimie","family":"Rogner","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumi","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareq A.","family":"Juratli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yokohama City University, Yokohama, Kanagawa Prefecture, Japan 236-0027;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara V. 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