Genotype-targeted local therapy of glioma
Year: 2018
Type: article
Abstract: Significance Lower-grade gliomas are often characterized by mutations in metabolism-related genes isocitrate dehydrogenase 1 ( IDH1 ) and IDH2 . 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.
Authors: Ganesh M. Shankar, Ameya R. Kirtane, Julie J. Miller, Hormoz Mazdiyasni, Jaimie Rogner, Tammy Tai, Erik A. Williams, Fumi Higuchi, Tareq A. Juratli, Kensuke Tateishi, Mara V. A. Koerner, Shilpa S. Tummala, Alexandria L. Fink, Tristan Penson, Stephen P. Schmidt, Gregory R. Wojtkiewicz, Aymen Baig, Joshua M. Francis, Mikael L. Rinne, Julie M. Batten, Tracy T. Batchelor, Priscilla K. Brastianos, William T. Curry, Fred G. Barker, Justin T. Jordan, A. John Iafrate, Andrew S. Chi, Jochen K. Lennerz, Matthew Meyerson, Robert Langer, Hiroaki Wakimoto, Giovanni Traverso, Daniel P. Cahill
Institutions: Harvard University, Massachusetts General Hospital, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, Center for Neuro-Oncology, Yokohama City University, Center for Systems Biology, Broad Institute, Dana-Farber Cancer Institute, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Brigham and Women's Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Controlled Release of Macromolecules, A new high-throughput gastrointestinal tract explant platform for drug formulation discovery and metabolic disease modulation, G458629407, Therapeutic strategy for IDH mutant gliomas by NAD+ depletion, G4936201288, G5797641063, G9000163483, Training Program in Nervous System Tumors, Targeted Therapies for Glioma
OpenAlex ID: W2886656428