Journal ArticleDOI
Predictive and prognostic markers in human glioblastomas.
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TLDR
A companion correlative study found that GBM patients with tumors with MGMT promoter methylation appeared to derive the greatest benefit from the addition of TMZ to radiation therapy, showing promise for the tailoring of future treatments according to the molecular and genetic profiles of an individual's tumor.Abstract:
Glioblastomas (GBMs) are among the most aggressive of all known human tumors. The median survival times remain in the 12- to 15-month range despite aggressive surgery, radiation, and chemotherapy. Through molecular and genetic profiling efforts, underlying mechanisms of resistance to these therapies are becoming better understood. The present standard of care has been shaped by the recently reported phase III study by the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada, which found that the addition of temozolomide (TMZ) to radiation therapy significantly improved outcome compared with radiation alone. However, careful examination of these data reveals that not all GBM patients benefited from the addition of TMZ to radiation therapy. A companion correlative study found that GBM patients with tumors with MGMT promoter methylation appeared to derive the greatest benefit from the addition of TMZ to radiation therapy. Although this finding is provocative, it should be kept in mind that this study was performed retrospectively and that prospective validation is required before MGMT methylation can be used for clinical stratification purposes. However, this study does show promise for the tailoring of future treatments according to the molecular and genetic profiles of an individual's tumor rather than using the "one-glove-fits-all" approach that is currently being followed. As more effective "smart drugs" are developed, molecular and genetic profiling will assume even greater importance in this regard.read more
Citations
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Journal ArticleDOI
Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme
Matthew J. McGirt,Khoi D. Than,Jon D. Weingart,Kaisorn L. Chaichana,Frank J. Attenello,Alessandro Olivi,John Laterra,Lawrence Kleinberg,Stuart A. Grossman,Henry Brem,Alfredo Quiñones-Hinojosa +10 more
TL;DR: Concomitant TMZ therapy in addition to Gliadel wafer implantation was associated with a median survival of nearly 21 months without increased perioperative morbidity, and Temozolomide can be safely administered to patients receiving GliAD wafers after resection of GBM.
Journal ArticleDOI
A ten-microRNA expression signature predicts survival in glioblastoma.
TL;DR: A miRNA expression signature that can predict GBM patient survival is identified and may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy.
Journal ArticleDOI
Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma
TL;DR: The various molecular mediators that regulate GBM angiogenesis are highlighted and summarized with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients.
Journal ArticleDOI
Therapeutic nanomedicine for brain cancer
TL;DR: This review discusses the obstacles to effective treatment that are currently faced in the field, as well as various nanomedicine techniques that have been used or are being explored to overcome them, with a focus on liposomal and polymeric nanoparticles.
Journal ArticleDOI
Glioblastoma multiforme: Molecular characterization and current treatment strategy (Review).
TL;DR: The molecular characterization of tumor cells, the current standard of care for patients diagnosed with GBM, including gross or near-total resection of the tumor, followed by radiotherapy, stereotactic brachytherapy, chemotherapy and new targeted therapies are reviewed to conclude that multimodal approaches for the treatment of patients with G BM may significantly improve their prognoses.
References
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Journal ArticleDOI
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi,Annie-Claire Diserens,Thierry Gorlia,Marie-France Hamou,Nicolas de Tribolet,Nicolas de Tribolet,Michael Weller,Johan M. Kros,Johannes A. Hainfellner,Warren P. Mason,Luigi Mariani,Jacoline E C Bromberg,Peter Hau,René O. Mirimanoff,J. Gregory Cairncross,Robert C. Janzer,Roger Stupp +16 more
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Journal ArticleDOI
Targeted Disruption of Mouse EGF Receptor: Effect of Genetic Background on Mutant Phenotype
David W. Threadgill,Andrzej A. Dlugosz,Laura A. Hansen,Tamar Tennenbaum,Ulrike Lichti,Della Yee,Christian LaMantia,Tracy Mourton,Karl Herrup,Raymond C. Harris,John A. Barnard,Stuart H. Yuspa,Robert J. Coffey,Terry Magnuson +13 more
TL;DR: The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities.
Journal ArticleDOI
Role of the insulin-like growth factor family in cancer development and progression
Herbert Yu,Thomas E. Rohan +1 more
TL;DR: Evidence suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth.
Journal ArticleDOI
Malignant glioma: Genetics and biology of a grave matter
Elizabeth A. Maher,Frank B. Furnari,Robert M. Bachoo,David H. Rowitch,David N. Louis,Webster K. Cavenee,Ronald A. DePinho +6 more
TL;DR: Although a comprehensive view of the genetic lesions encountered in malignant gliomas has been compiled, substantive conceptual and practical barriers remain in assigning functional significance to these genetic changes and in harnessing this basic information into the development of drugs that make a difference in patient care.
Journal ArticleDOI
Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor
Päivi J. Miettinen,Joel E. Berger,Juanito J. Meneses,Yume Phung,Roger A. Pedersen,Zena Werb,Rik Derynck +6 more
TL;DR: It is found that EGF-R-/- mice survive for up to 8 days after birth and suffer from impaired epithelial development in several organs, including skin, lung and gastrointestinal tract.
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