Overcoming therapeutic resistance in glioblastoma: the way forward
Satoru Osuka and Erwin G. Van Meir
Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Address correspondence to: Erwin G. Van Meir, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, C5078, Atlanta, Georgia 30322, USA. Phone: 404.778.5563; E-mail: evanmei@emory.edu.
Find articles by Osuka, S. in: JCI | PubMed | Google Scholar
Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Address correspondence to: Erwin G. Van Meir, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, C5078, Atlanta, Georgia 30322, USA. Phone: 404.778.5563; E-mail: evanmei@emory.edu.
Find articles by Van Meir, E. in: JCI | PubMed | Google Scholar
First published February 1, 2017 - More info
J Clin Invest. 2017;127(2):415–426. doi:10.1172/JCI89587.
Copyright © 2017, American Society for Clinical Investigation
Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Patients die from recurrent tumors that have become resistant to therapy. New strategies are needed to design future therapies that target resistant cells. Recent genomic studies have unveiled the complexity of tumor heterogeneity in glioblastoma and provide new insights into the genomic landscape of tumor cells that survive and initiate tumor recurrence. Resistant cells also co-opt developmental pathways and display stem-like properties; hence we propose to name them recurrence-initiating stem-like cancer (RISC) cells. Genetic alterations and genomic reprogramming underlie the innate and adaptive resistance of RISC cells, and both need to be targeted to prevent glioblastoma recurrence.
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