Chemoresistance in gliomas

Abstract

Despite improved knowledge and advanced treatments of gliomas, the overall survival rate for glioma patients remains low. Gliomas comprise of significant cell heterogeneity that contains a large number of multidrug resistant (MDR) phenotypes and cancer stem cells (CSCs), a combination that may contribute to the resistance to treatment. This article reviews the MDR related genes, major-vault protein (MVP), anti-apoptotic protein (Bcl-2) and the molecular mechanisms that may contribute to chemoresistance, in addition to the upregulated MDR phenotypes present in CSCs that has recently been identified in gliomas. Moreover, future potential therapies that modulate MDR phenotypes and CSCs are also reviewed. An improved understanding of MDR may lead to a combined treatment, targeting both CSCs and their protective MDR phenotypes leading eventually to attractive strategies for the treatment of gliomas.

Standard of care therapy for malignant glioma and its effect on tumor and stromal cells

“…However, the potential contribution of microglia produced NO to the tumor stem cell phenotype that has yet to be explored. It has also been shown that glioma stem-like cells express multi-drug resistance proteins such as ABCG2 and P-gp (Lu and Shervington, 2008;Bleau et al, 2009;Wang et al, 2010); hence, these cells tend to be highly resistant to cytotoxic drug therapy (Charles and Holland, 2009 (Dix et al, 1999). Signaling through CXCL12-CXCR4 is known to recruit Tregs to bone marrow and may also be involved in the recruitment of Tregs to brain tumors (Zhou et al, 2002;Grauer et al, 2007).…”

Glioma Stem Cells: Cell Culture, Markers and Targets for New Combination Therapies

“…Another feature that normal stem cells and glioma stem cells share is expression of drug efflux pumps. Adenosine triphosphate-binding cassette (ABC) pumps, ABCG2 and Pglycoprotein are expressed on glioma stem cells and are responsible for efflux of the fluorescent Hoechst 33342 dye, leading to the side population, which is enriched in glioma stem cells (Lu and Shervington, 2008). However, in a model system, ABCG2-positive andnegative cells showed no difference in tumor formation in mice (Patrawala et al, 2005).…”

Stem cells and models of astrocytomas

“…BCRP1 is a member of the ATP binding cassette (ABC) transporters comprising of 48 members. 97 These transporters traffic molecules such as lipids and xenobiotic compounds across the cell membrane in an ATP dependent mechanism 97 . Another gene is MGMT, which is required to repair O 6 -methylguanine DNA induced damage by drugs such as temozolomide.…”