Glioblastomas are the most frequent and malignant brain tumor hallmarked by aninvariably poor prognosis. They have been classically differentiated into primaryisocitrate dehydrogenase 1 or 2 (IDH1 -2) wild-type (wt) glioblastoma (GBM) andsecondary IDH mutant GBM, with IDH wt GBMs being commonly associated with olderage and poor prognosis. Recently, genetic analyses have been integrated with epigeneticinvestigations, strongly implementing typing and subtyping of brain tumors, includingGBMs, and leading to the new WHO 2021 classification. GBM genomic and epigenomicprofile influences evolution, resistance, and therapeutic responses. However, differentlyfrom other tumors, there is a wide gap between the refined GBM profiling and the limitedtherapeutic opportunities. In addition, the different oncogenes and tumor suppressorgenes involved in glial cell transformation, the heterogeneous nature of cancer, and therestricted access of drugs due to the blood–brain barrier have limited clinicaladvancements. This review will summarize the more relevant genetic alterations foundin GBMs and highlight their potential role as potential therapeutic targets.
Looking Beyond the Glioblastoma Mask: Is Genomics the Right Path?
Del Gaudio, Nunzio;
2022-01-01
Abstract
Glioblastomas are the most frequent and malignant brain tumor hallmarked by aninvariably poor prognosis. They have been classically differentiated into primaryisocitrate dehydrogenase 1 or 2 (IDH1 -2) wild-type (wt) glioblastoma (GBM) andsecondary IDH mutant GBM, with IDH wt GBMs being commonly associated with olderage and poor prognosis. Recently, genetic analyses have been integrated with epigeneticinvestigations, strongly implementing typing and subtyping of brain tumors, includingGBMs, and leading to the new WHO 2021 classification. GBM genomic and epigenomicprofile influences evolution, resistance, and therapeutic responses. However, differentlyfrom other tumors, there is a wide gap between the refined GBM profiling and the limitedtherapeutic opportunities. In addition, the different oncogenes and tumor suppressorgenes involved in glial cell transformation, the heterogeneous nature of cancer, and therestricted access of drugs due to the blood–brain barrier have limited clinicaladvancements. This review will summarize the more relevant genetic alterations foundin GBMs and highlight their potential role as potential therapeutic targets.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
