Toward precision medicine in glioblastoma: the promise and the challenges

Abstract

Integrated sequencing strategies have provided a broader understanding of the genomic landscape and molecular classifications of multiple cancer types and have identified various therapeutic opportunities across cancer subsets. Despite pivotal advances in the characterization of genomic alterations in glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. In this review, we highlight potential reasons why targeting single alterations has yielded limited clinical efficacy in glioblastoma, focusing on issues of tumor heterogeneity and pharmacokinetic failure. We outline strategies to address these challenges in applying precision medicine to glioblastoma and the rationale for applying targeted combination therapy approaches that match genomic alterations with compounds accessible to the central nervous system.

Multi-omics analysis of primary glioblastoma cell lines shows recapitulation of pivotal molecular features of parental tumors

“…Despite intensive treatments (ie, surgery, radiation therapy, and/ or chemotherapy), prognosis of GBM patients remains dismal, with a median overall survival between 12 and 18 months appealing for new treatments. 1 Most of the innovative therapeutic strategies for cancer treatment developed in the last decade incorporate drugs targeting specific oncogenic proteins or signaling pathways. Such promising approaches are already used in non-CNS tumors.…”

Foods as a Novel Treatment for Glioblastoma

“…[7] Although different types of cancer therapy have been applied for glioblastoma, the 5-year survival rate of patient is less than 10% because of heterogeneous complex tissue of glioblastoma, genetic mutations, and abnormal signal pathways. [8,9] Recently, novel therapeutic approaches evaluated the molecular characteristics of glioblastoma by setting of Glio-Tex project (GBM and Experimental Therapeutics) a GBM patient-derived cell line (GBM-PDCL) library. [10] Nowadays, metabolic pathways have been on attention of scientists for treatment of glioblastoma tumor cells are depend on anaerobic glycolysis to get their energy sources and they are not able to uptake glucose to provide their energy needs; However, the Apolipoprotein MOrtality RISk (AMORIS) data showed a paradoxical result which observed a reverse correlation between glucose consumption and glioma.…”

Pharmacotherapies for the treatment of glioblastoma – current evidence and perspectives

“…A detailed discussion of these strategies, recently provided [9], would be beyond the scope of this review. Most concepts were not developed beyond phase II because of disappointing…”

“…Main challenges in developing efficacious pharmacotherapies for glioblastoma include high genetic heterogeneity within the tumor and between different patients, rapid development of drug resistance and poor distribution of most drugs within the brain [8,9].…”