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REVIEW

Malignant astrocytic glioma: genetics, biology, and paths to treatment

¹ Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA; ² Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA; ³ Cancer Center University of California at San Diego, La Jolla, California 92093, USA; ⁴ Department of Neurology and Department of Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75390, USA; ⁵ Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts 02115, USA; ⁶ Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts 02115, USA; ⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts 02115, USA; ⁸ Department of Medicine and Department of Genetics Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts 02115, USA; ⁹ Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts 02115, USA; ¹⁰ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussetts 02115, USA; ¹¹ Department of Neurosurgery, Memorial Sloan Kettering Cancer Institute, New York, New York 10065, USA; ¹² Department of Dermatology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts 02115, USA; ¹³ Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093, USA

Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses.

[Keywords: Glioma; glioblastoma; neural stem cells; cancer stem cells; tyrosine kinase inhibitor; genetically engineered models]]

E-MAIL ron_depinho{at}dfci.harvard.edu; FAX (617) 632-6069.

¹⁵ E-MAIL wcavenee{at}ucsd.edu; FAX (858) 534-7750.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1596707

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