Translating biology into clinic: the case of glioblastoma

被引:16
作者
Lino, Maddalena
Merlo, Adrian [1 ]
机构
[1] Univ Basel Hosp, Mol Neurooncol Lab, CH-4031 Basel, Switzerland
关键词
GROWTH-FACTOR RECEPTOR; STEM-CELL; PATHWAY ACTIVATION; MALIGNANT GLIOMAS; DNA-REPAIR; INHIBITION; GENE; HYPERMETHYLATION; MICRORNA-21; APOPTOSIS;
D O I
10.1016/j.ceb.2008.12.009
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
GBM, the most common,and malignant primary tumor of the CNS, is characterized by exponential growth and diffuse invasiveness. Although the diverse causative genotypes that give rise to a inhomogeneous histological phenotype are well defined, effective therapy inducing tumor cell apoptosis has not been established so far. Following surgery, billions of invasive tumor cells remain to be targeted by systemic and local therapies. Targeting non-overlapping pathways, rather than a single agent approach, is more likely to be effective. The potential of local drug application has not been exploited yet. Systemically, novel drug combinations have to be developed that not only target key molecules at the signaling crossroads but also exploit energy demand and the epigenetic cancer program of GBM.
引用
收藏
页码:311 / 316
页数:6
相关论文
共 48 条
[1]   Epidermal growth factor receptor and Ink4a/Arf:: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis [J].
Bachoo, RM ;
Maher, EA ;
Ligon, KL ;
Sharpless, NE ;
Chan, SS ;
You, MJJ ;
Tang, Y ;
DeFrances, J ;
Stover, E ;
Weissleder, R ;
Rowitch, DH ;
Louis, DN ;
DePinho, RA .
CANCER CELL, 2002, 1 (03) :269-277
[2]   Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].
Bao, Shideng ;
Wu, Qiulian ;
McLendon, Roger E. ;
Hao, Yueling ;
Shi, Qing ;
Hjelmeland, Anita B. ;
Dewhirst, Mark W. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
NATURE, 2006, 444 (7120) :756-760
[3]   An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].
Ben-Porath, Ittai ;
Thomson, Matthew W. ;
Carey, Vincent J. ;
Ge, Ruping ;
Bell, George W. ;
Regev, Aviv ;
Weinberg, Robert A. .
NATURE GENETICS, 2008, 40 (05) :499-507
[4]   Anticancer activities of histone deacetylase inhibitors [J].
Bolden, Jessica E. ;
Peart, Melissa J. ;
Johnstone, Ricky W. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784
[5]   Loss of NOTCH2 Positively Predicts Survival in Subgroups of Human Glial Brain Tumors [J].
Boulay, Jean-Louis ;
Miserez, Andre R. ;
Zweifel, Christian ;
Sivasankaran, Balasubramanian ;
Kana, Veronika ;
Ghaffari, Anthony ;
Luyken, Cordelia ;
Sabel, Michael ;
Zerrouqi, Abdessamad ;
Wasner, Morten ;
Van Meir, Erwin ;
Tolnay, Markus ;
Reifenberger, Guido ;
Merlo, Adrian .
PLOS ONE, 2007, 2 (06)
[6]  
Carracedo A, 2008, J CLIN INVEST, V118, P3065, DOI [10.1172/jCI34739, 10.1172/JCI34739]
[7]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[8]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[9]   Extensive modulation of a set of microRNAs in primary glioblastoma [J].
Ciafrè, SA ;
Galardi, S ;
Mangiola, A ;
Ferracin, M ;
Liu, CG ;
Sabatino, G ;
Negrini, M ;
Maira, G ;
Croce, CM ;
Farace, MG .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (04) :1351-1358
[10]  
Davis F G, 2001, Expert Rev Anticancer Ther, V1, P395, DOI 10.1586/14737140.1.3.395