Molecular predictors in glioblastoma: toward personalized therapy.

Recent therapeutic advances have improved standard treatment for patients with newly diagnosed glioblastoma. Unfortunately, even with these improvements, only a fraction of patients derive significant benefit and experience prolonged survival. These findings are consistent with long-standing clinical and recent molecular evidence that subtypes of glioblastoma exist with differing survival rates and response to treatment. However, patients with newly diagnosed glioblastoma are currently treated in a uniform fashion, without regard for potential underlying differences in molecular alterations or prognosis. In this review, we will discuss recent progress toward the identification of robust and clinically relevant molecular subgroups of glioblastoma and initial steps in using this information to individualize therapy and overcome treatment resistance.

[1]  J. McNamara Cancer Stem Cells , 2007, Methods in Molecular Biology.

[2]  J. Dick,et al.  A human colon cancer cell capable of initiating tumour growth in immunodeficient mice , 2007, Nature.

[3]  Mark W. Dewhirst,et al.  Glioma stem cells promote radioresistance by preferential activation of the DNA damage response , 2006, Nature.

[4]  K. Black,et al.  Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma , 2006, Molecular Cancer.

[5]  Irving L Weissman,et al.  Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. , 2006, Cancer research.

[6]  M. Noble,et al.  Cancer stem cells. , 2006, The New England journal of medicine.

[7]  Koji Yoshimoto,et al.  Primary Glioblastomas Express Mesenchymal Stem-Like Properties , 2006, Molecular Cancer Research.

[8]  Li Zhang,et al.  Prognostic Associations of Activated Mitogen-Activated Protein Kinase and Akt Pathways in Glioblastoma , 2006, Clinical Cancer Research.

[9]  Yuri Kotliarov,et al.  Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. , 2006, Cancer cell.

[10]  Thomas D. Wu,et al.  Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. , 2006, Cancer cell.

[11]  Tak W. Mak,et al.  Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis , 2006, Nature Reviews Cancer.

[12]  J. Rosen,et al.  Stem cells in the etiology and treatment of cancer. , 2006, Current opinion in genetics & development.

[13]  A. Verma MGMT Gene Silencing and Benefit From Temozolomide in Glioblastoma , 2006 .

[14]  Maqc Consortium The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements , 2006, Nature Biotechnology.

[15]  G. Cavet,et al.  Epithelial versus Mesenchymal Phenotype Determines In vitro Sensitivity and Predicts Clinical Activity of Erlotinib in Lung Cancer Patients , 2005, Clinical Cancer Research.

[16]  Alfonso Bellacosa,et al.  Epithelial–mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways , 2005, Oncogene.

[17]  Koji Yoshimoto,et al.  Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. , 2005, The New England journal of medicine.

[18]  E. Brown,et al.  Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. , 2005, Cancer research.

[19]  Richard Simon,et al.  Roadmap for developing and validating therapeutically relevant genomic classifiers. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  H. Beug,et al.  Molecular requirements for epithelial-mesenchymal transition during tumor progression. , 2005, Current opinion in cell biology.

[21]  M. Berger,et al.  Biomarkers to Predict Response to Epidermal Growth Factor Receptor Inhibitors , 2005, Cell cycle.

[22]  J. Dick,et al.  Cancer stem cells: lessons from leukemia. , 2005, Trends in cell biology.

[23]  Jiri Zavadil,et al.  TGF-β and epithelial-to-mesenchymal transitions , 2005, Oncogene.

[24]  M. West,et al.  Gene expression profiling and genetic markers in glioblastoma survival. , 2005, Cancer research.

[25]  K. Aldape,et al.  YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma , 2005, Clinical Cancer Research.

[26]  Michael Dean,et al.  Tumour stem cells and drug resistance , 2005, Nature Reviews Cancer.

[27]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[28]  K. Aldape,et al.  Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. , 2005, Cancer research.

[29]  David J. Yang,et al.  Prognostic Effect of Epidermal Growth Factor Receptor and EGFRvIII in Glioblastoma Multiforme Patients , 2005, Clinical Cancer Research.

[30]  J. Zavadil,et al.  TGF-beta and epithelial-to-mesenchymal transitions. , 2005, Oncogene.

[31]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[32]  D. Farkas,et al.  Isolation of cancer stem cells from adult glioblastoma multiforme , 2004, Oncogene.

[33]  R. Henkelman,et al.  Identification of human brain tumour initiating cells , 2004, Nature.

[34]  F. DiMeco,et al.  Erratum: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma (Cancer Research (October 2004) 64 (7011-7021) , 2004 .

[35]  Ugo Orfanelli,et al.  Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma , 2004, Cancer Research.

[36]  P. Dirks,et al.  Cancer stem cells in nervous system tumors , 2004, Oncogene.

[37]  S. Horvath,et al.  Gene Expression Profiling of Gliomas Strongly Predicts Survival , 2004, Cancer Research.

[38]  Caterina Giannini,et al.  Immunohistochemical Detection of EGFRvIII in High Malignancy Grade Astrocytomas and Evaluation of Prognostic Significance , 2004, Journal of neuropathology and experimental neurology.

[39]  Alona Muzikansky,et al.  The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  D. Bigner,et al.  Development of novel targeted therapies in the treatment of malignant glioma , 2004, Nature Reviews Drug Discovery.

[41]  D. Ransohoff Rules of evidence for cancer molecular-marker discovery and validation , 2004, Nature Reviews Cancer.

[42]  Tony Hunter,et al.  Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. , 2003, Cancer cell.

[43]  Cynthia Hawkins,et al.  Identification of a cancer stem cell in human brain tumors. , 2003, Cancer research.

[44]  T. Golub,et al.  Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. , 2003, Cancer research.

[45]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  J. Thiery Epithelial–mesenchymal transitions in tumour progression , 2002, Nature Reviews Cancer.

[47]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.

[48]  R. DePinho,et al.  Malignant glioma: genetics and biology of a grave matter. , 2001, Genes & development.

[49]  Susan M. Chang,et al.  Glioblastoma Patients Epidermal Growth Factor Receptor , and Survival in Analysis of Complex Relationships between Age , p 53 , Updated , 2001 .

[50]  D. Louis,et al.  Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. , 1998, Journal of the National Cancer Institute.

[51]  B. Scheithauer,et al.  The Glial and Mesenchymal Elements of Gliosarcomas Share Similar Genetic Alterations , 1996, Journal of neuropathology and experimental neurology.

[52]  M. Caligiuri,et al.  A cell initiating human acute myeloid leukaemia after transplantation into SCID mice , 1994, Nature.

[53]  M A Richards,et al.  Node negative breast cancer. , 1990, BMJ.