TY - JOUR
T1 - GBM's multifaceted landscape
T2 - Highlighting regional and microenvironmental heterogeneity
AU - Vartanian, Alenoush
AU - Singh, Sanjay K.
AU - Agnihotri, Sameer
AU - Jalali, Shahrzad
AU - Burrell, Kelly
AU - Aldape, Kenneth D.
AU - Zadeh, Gelareh
PY - 2014/9
Y1 - 2014/9
N2 - Gliomas are a heterogeneous group of tumors that show variable proliferative potential, invasiveness, aggressiveness, histological grading, and clinical behavior. In this review, we focus on glioblastoma multiforme (GBM), a grade IV glioma, which is the most common and malignant of primary adult brain tumors. Research over the past several decades has revealed the existence of extensive cellular, molecular, genetic, epigenetic, and metabolic heterogeneity among tumors of the same grade and even within individual tumors. Evaluation of different tumor types has shown that tumors with advanced grade and clinical aggressiveness also display enhanced molecular, cellular, and microenvironmental heterogeneity. From a therapeutic standpoint, this heterogeneity is a major clinical hurdle for devising effective therapeutic strategies for patients and challenges personalized medicine. In this review, we will highlight key aspects of GBM heterogeneity, directing special attention to regional heterogeneity, hypoxia, genomic heterogeneity, tumor-specific metabolic reprogramming, neovascularization or angiogenesis, and stromal immune cells. We will further discuss the clinical implications of GBM heterogeneity in the context of therapy.
AB - Gliomas are a heterogeneous group of tumors that show variable proliferative potential, invasiveness, aggressiveness, histological grading, and clinical behavior. In this review, we focus on glioblastoma multiforme (GBM), a grade IV glioma, which is the most common and malignant of primary adult brain tumors. Research over the past several decades has revealed the existence of extensive cellular, molecular, genetic, epigenetic, and metabolic heterogeneity among tumors of the same grade and even within individual tumors. Evaluation of different tumor types has shown that tumors with advanced grade and clinical aggressiveness also display enhanced molecular, cellular, and microenvironmental heterogeneity. From a therapeutic standpoint, this heterogeneity is a major clinical hurdle for devising effective therapeutic strategies for patients and challenges personalized medicine. In this review, we will highlight key aspects of GBM heterogeneity, directing special attention to regional heterogeneity, hypoxia, genomic heterogeneity, tumor-specific metabolic reprogramming, neovascularization or angiogenesis, and stromal immune cells. We will further discuss the clinical implications of GBM heterogeneity in the context of therapy.
KW - Angiogenesis
KW - Glioblastoma
KW - Hypoxia
KW - Metabolism
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U2 - 10.1093/neuonc/nou035
DO - 10.1093/neuonc/nou035
M3 - Review article
C2 - 24642524
AN - SCOPUS:84905917573
SN - 1522-8517
VL - 16
SP - 1167
EP - 1175
JO - Neuro-oncology
JF - Neuro-oncology
IS - 9
ER -