title: How to train glioma cells to die: molecular challenges in cell death.
abstract: The five-year survival rate for patients with malignant glioma is less than 10%. Despite aggressive chemo/radiotherapy these tumors have remained resistant to almost every interventional strategy evaluated in patients. Resistance to these agents is attributed to extrinsic mechanisms such as the tumor microenvironment, poor drug penetration, and tumoral heterogeneity. In addition, genetic and molecular examination of these tumors has revealed defective apoptotic regulation, enhanced pro-survival autophagy signaling, and a propensity for necrosis that aids in the adaptation to environmental stress and resistance to treatment. The combination of extrinsic and intrinsic hallmarks in glioma contributes to the multifaceted resistance to traditional anti-tumor agents. Here we describe the biology of the disease relevant to therapeutic resistance, with a specific focus on molecular deregulation of cell death pathways. Emerging studies investigating the targeting of these pathways including BH3 mimetics and autophagy inhibitors that are being evaluated in both the preclinical and clinical settings are discussed. This review highlights the pathways exploited by glioblastoma cells that drive their hallmark pro-survival predisposition and makes therapy development such a challenge.
authors.affiliation: Department of Neurological Surgery, The Ohio State University Medical Center, 385-B OSUCCC, 410 West 12th Avenue, Columbus, OH, 43210, USA.|Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, 27710, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wojton
authors.affiliation: Department of Neurological Surgery, The Ohio State University Medical Center, 385-B OSUCCC, 410 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Walter Hans
authors.initials: WH
authors.lastname: Meisen
authors.affiliation: Department of Neurological Surgery, The Ohio State University Medical Center, 385-B OSUCCC, 410 West 12th Avenue, Columbus, OH, 43210, USA. balveen.kaur@osumc.edu.
authors.forename: Balveen
authors.initials: B
authors.lastname: Kaur
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology*; D005910:Glioma / Q000473:pathology*; D006801:Humans
keywords: Apoptosis; Autophagy; Glioma; Necrosis; Resistance