Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Neurol. Sep 28, 2015; 5(3): 88-101
Published online Sep 28, 2015. doi: 10.5316/wjn.v5.i3.88
Molecular pathogenesis of glioblastoma multiforme: Nuances, obstacles, and implications for treatment
Siddharth K Joshi, Nevena Lucic, Richard Zuniga
Siddharth K Joshi, Department of Medicine, New York Methodist Hospital, Brooklyn, NY 11215, United States
Nevena Lucic, Richard Zuniga, Division of Hematology/Oncology, Department of Medicine, New York Methodist Hospital, Brooklyn, NY 11215, United States
Author contributions: Joshi SK, Lucic N and Zuniga R contributed to this paper.
Conflict-of-interest statement: The authors have no conflicts of interest to state related to this work being submitted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Richard Zuniga, MD, Division of Hematology/Oncology, Department of Medicine, New York Methodist Hospital, 506 6th Street, Brooklyn, NY 11215, United States. rickzunigaperu@hotmail.com
Telephone: +1-718-2081820 Fax: +1-718-2081822
Received: September 29, 2014
Peer-review started: October 2, 2014
First decision: December 12, 2014
Revised: July 7, 2015
Accepted: July 21, 2015
Article in press: July 23, 2015
Published online: September 28, 2015
Abstract

Glioblastoma multiforme (GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology and medicine. Historically this may be contextualized in the fact that the medical and scientific communities have had a very elementary understanding of its intricate and complex pathophysiology. The last 10-15 years have yielded a number of studies that have elucidated much of the molecular and genetic complexities of GBM that underlie its pathogenesis. Excitingly, some of these discovered genetic mutations and molecular profiles in GBM have demonstrated value in prognostication and utility in predicting response to treatment. Despite this, however, treatment options for patients have remained somewhat limited. These treatment options are expected to expand with the availability of new data and with the transition of novel treatment modalities from animal to human studies. This paper will have a threefold objective: provide an overview of the traditional paradigm in understanding and treating GBM, describe recent discoveries in the molecular pathogenesis of GBM against this historical backdrop, and acquaint the reader with new treatment modalities that hold significant therapeutic potential for patients.

Keywords: Molecular pathogenesis, Temozolomide, Glioblastoma multiforme, Treatment resistance, Hypoxia, Recurrent glioblastoma multiforme, Bevacizumab

Core tip: This paper provides the reader with an overview some of the primary molecular markers that are implicated in the pathogenesis glioblastoma multiforme (GBM). It provides a robust review of the evidence that supports the use of these molecular markers for both prognostication and prediction for response to treatment. It gives the reader context for understanding the hypoxia model and how it informs treatment resistance in GBM. It provides an overview of cancer stem cells and their role in GBM biology. And it acquaints the reader with a few of the new, promising treatment modalities that are emerging.