This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reardon, D. A. Articles by Bigner, D. D. Search for Related Content PubMed PubMed Citation Articles by Reardon, D. A. Articles by Bigner, D. D. Social Bookmarking                            What's this?

Recent Advances in the Treatment of Malignant Astrocytoma

From the Departments of Surgery, Pediatrics, and Pathology, Duke University Medical Center, Durham, NC

Address reprint requests to David A. Reardon, the Preston Robert Tisch Brain Tumor Center at Duke University, Duke University Medical Center, Box 3624, Durham, NC 27710; e-mail: reard003{at}mc.duke.edu

Malignant gliomas, including the most common subtype, glioblastoma multiforme (GBM), are among the most devastating of neoplasms. Their aggressive infiltration in the CNS typically produces progressive and profound disability—ultimately leading to death in nearly all cases. Improvement in outcome has been elusive despite decades of intensive clinical and laboratory research. Surgery and radiotherapy, the traditional cornerstones of therapy, provide palliative benefit, while the value of chemotherapy has been marginal and controversial. Limited delivery and tumor heterogeneity are two fundamental factors that have critically hindered therapeutic progress. A novel chemoradiotherapy approach, consisting of temozolomide administered concurrently during radiotherapy followed by adjuvant systemic temozolomide, has recently demonstrated a meaningful, albeit modest, improvement in overall survival for newly diagnosed GBM patients. As cell-signaling alterations linked to the development and progression of gliomas are being increasingly elucidated, targeted therapies have rapidly entered preclinical and clinical evaluation. Responses to therapies that function via DNA damage have been associated with specific mediators of resistance that may also be subject to targeted therapies. Other approaches include novel locoregional delivery techniques to overcome barriers of delivery. The simultaneous development of multiple advanced therapies based on specific tumor biology may finally offer glioma patients improved survival.

Supported by National Institutes of Health Grants No. NS20023, CA11898, and MO1 RR 30, General Clinical Research Centers Program, National Center for Research Resources, National Cancer Institute Grant No. SPORE 1 P20 CA096890, and additional funding support from the Pediatric Brain Tumor Foundation of the United States and the Accelerate Brain Cancer Cure (ABC 2) Foundation.

Authors' disclosures of potential conflicts of interest and author contributors are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Spiegl-Kreinecker, C. Pirker, M. Filipits, D. Lotsch, J. Buchroithner, J. Pichler, R. Silye, S. Weis, M. Micksche, J. Fischer, et al. O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients Neuro Oncology, October 15, 2009; (2009) nop003v1. [Abstract] [Full Text] [PDF]

				S. Paternot and P. P. Roger Combined Inhibition of MEK and Mammalian Target of Rapamycin Abolishes Phosphorylation of Cyclin-Dependent Kinase 4 in Glioblastoma Cell Lines and Prevents Their Proliferation Cancer Res., June 1, 2009; 69(11): 4577 - 4581. [Abstract] [Full Text] [PDF]

				C. Mikelis, E. Sfaelou, M. Koutsioumpa, N. Kieffer, and E. Papadimitriou Integrin {alpha}{nu}{beta}3 is a pleiotrophin receptor required for pleiotrophin-induced endothelial cell migration through receptor protein tyrosine phosphatase {beta}/{zeta} FASEB J, May 1, 2009; 23(5): 1459 - 1469. [Abstract] [Full Text] [PDF]

				H. Zheng, H. Ying, H. Yan, A.C. Kimmelman, D.J. Hiller, A.-J. Chen, S.R. Perry, G. Tonon, G.C. Chu, Z. Ding, et al. Pten and p53 Converge on c-Myc to Control Differentiation, Self-renewal, and Transformation of Normal and Neoplastic Stem Cells in Glioblastoma Cold Spring Harb Symp Quant Biol, January 15, 2009; (2009) sqb.2008.73.047v1. [Abstract] [PDF]

				Q. Zhou and J. M. Gallo Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model Neuro-oncol, January 1, 2009; 11(3): 301 - 310. [Abstract] [Full Text] [PDF]

				H.-W. Lo, X. Cao, H. Zhu, and F. Ali-Osman Constitutively Activated STAT3 Frequently Coexpresses with Epidermal Growth Factor Receptor in High-Grade Gliomas and Targeting STAT3 Sensitizes Them to Iressa and Alkylators Clin. Cancer Res., October 1, 2008; 14(19): 6042 - 6054. [Abstract] [Full Text] [PDF]

				L. W Buie and J. Valgus Bevacizumab: A Treatment Option for Recurrent Glioblastoma Multiforme Ann. Pharmacother., October 1, 2008; 42(10): 1486 - 1490. [Abstract] [Full Text] [PDF]

				D. S. Ziegler, A. L. Kung, and M. W. Kieran Anti-Apoptosis Mechanisms in Malignant Gliomas J. Clin. Oncol., January 20, 2008; 26(3): 493 - 500. [Abstract] [Full Text] [PDF]

				A. Claes, P. Wesseling, J. Jeuken, C. Maass, A. Heerschap, and W. P.J. Leenders Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization Mol. Cancer Ther., January 1, 2008; 7(1): 71 - 78. [Abstract] [Full Text] [PDF]

				H. Aoki, T. Yokoyama, K. Fujiwara, A. M. Tari, R. Sawaya, D. Suki, K. R. Hess, K. D. Aldape, S. Kondo, R. Kumar, et al. Phosphorylated Pak1 Level in the Cytoplasm Correlates with Shorter Survival Time in Patients with Glioblastoma Clin. Cancer Res., November 15, 2007; 13(22): 6603 - 6609. [Abstract] [Full Text] [PDF]

				M. M. Alonso, M. Cascallo, C. Gomez-Manzano, H. Jiang, B. N. Bekele, A. Perez-Gimenez, F. F. Lang, Y. Piao, R. Alemany, and J. Fueyo ICOVIR-5 Shows E2F1 Addiction and Potent Antiglioma Effect In vivo Cancer Res., September 1, 2007; 67(17): 8255 - 8263. [Abstract] [Full Text] [PDF]

				J. B. Axelsen, J. Lotem, L. Sachs, and E. Domany Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles PNAS, August 7, 2007; 104(32): 13122 - 13127. [Abstract] [Full Text] [PDF]

				A. Iwamaru, E. Iwado, S. Kondo, R. A. Newman, B. Vera, A. D. Rodriguez, and Y. Kondo Eupalmerin acetate, a novel anticancer agent from Caribbean gorgonian octocorals, induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway Mol. Cancer Ther., January 1, 2007; 6(1): 184 - 192. [Abstract] [Full Text] [PDF]

				L. Goldberg and Y. Kloog A Ras Inhibitor Tilts the Balance between Rac and Rho and Blocks Phosphatidylinositol 3-Kinase-Dependent Glioblastoma Cell Migration Cancer Res., December 15, 2006; 66(24): 11709 - 11717. [Abstract] [Full Text] [PDF]

				N. Redjal, J. A. Chan, R. A. Segal, and A. L. Kung CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas. Clin. Cancer Res., November 15, 2006; 12(22): 6765 - 6771. [Abstract] [Full Text] [PDF]

				S. Pellegatta, P. L. Poliani, D. Corno, F. Menghi, F. Ghielmetti, B. Suarez-Merino, V. Caldera, S. Nava, M. Ravanini, F. Facchetti, et al. Neurospheres Enriched in Cancer Stem-Like Cells Are Highly Effective in Eliciting a Dendritic Cell-Mediated Immune Response against Malignant Gliomas Cancer Res., November 1, 2006; 66(21): 10247 - 10252. [Abstract] [Full Text] [PDF]

				C. Grommes, G. E. Landreth, M. Sastre, M. Beck, D. L. Feinstein, A. H. Jacobs, U. Schlegel, and M. T. Heneka Inhibition of in Vivo Glioma Growth and Invasion by Peroxisome Proliferator-Activated Receptor {gamma} Agonist Treatment Mol. Pharmacol., November 1, 2006; 70(5): 1524 - 1533. [Abstract] [Full Text] [PDF]

				J. A. McCubrey, M. M. LaHair, and R. A. Franklin OSU-03012 in the Treatment of Glioblastoma Mol. Pharmacol., August 1, 2006; 70(2): 437 - 439. [Abstract] [Full Text] [PDF]

				T. S. Lawrence, J. C. Buckner, and F. F. Lang CNS Malignancies: At Last, Real Progress J. Clin. Oncol., March 10, 2006; 24(8): 1225 - 1227. [Full Text] [PDF]