Molecular Markers of Therapy-Resistant Glioblastoma and Potential Strategy to Combat Resistance

Abstract

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. With its overall dismal prognosis (the median survival is 14 months), GBMs demonstrate a resounding resilience against all current treatment modalities. The absence of a major progress in the treatment of GBM maybe a result of our poor understanding of both GBM tumor biology and the mechanisms underlying the acquirement of treatment resistance in recurrent GBMs. A comprehensive understanding of these markers is mandatory for the development of treatments against therapy-resistant GBMs. This review also provides an overview of a novel marker called acid ceramidase and its implication in the development of radioresistant GBMs. Multiple signaling pathways were found altered in radioresistant GBMs. Given these global alterations of multiple signaling pathways found in radioresistant GBMs, an effective treatment for radioresistant GBMs may require a cocktail containing multiple agents targeting multiple cancer-inducing pathways in order to have a chance to make a substantial impact on improving the overall GBM survival.

OSgbm: An Online Consensus Survival Analysis Web Server for Glioblastoma

“…Previous studies have reported some prognostic biomarkers in GBM, such as gene mutation of gene IDH and PTEN, and expression variation of gene CD133 (Yang et al, 2016;Cai and Sughrue, 2017;Nguyen et al, 2018). However, these biomarkers have not been translated to clinical applications due to the lack of independent validation.…”

Genomic and Transcriptomic Characterization of the New Human Glioblastoma Cell Line AHOL1

“…Massive amounts of cancer genomics data generated from next-generation sequencing have motivated investigators to develop novel computational approaches for the identification of new druggable genes, which can be used as therapeutic targets in the precision cancer medicine [85]. Our AHOL1 genomic data showed that nine genes (HCRTR2; ETV1; PTPRD; PRKX; STS; RPS6KA6; ZFY; USP9Y and KDM5D) are known as potential druggable anticancer targets, and some of them could be druggable vulnerabilities in some subtypes of GBM [86]. Together, these studies have highlighted the great potential of AHOL1 cell line for in vitro studies.…”

Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen

“…3. A consensus has formed within the GB research community that "an effective treatment targeting radioresistant GBM may require a cocktail containing multiple agents targeting multiple implicated pathways...given the [dozens of] global alterations of multiple signaling pathways found in radioresistant [and chemoresistant] GBMs" [62].…”