Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response

Article ID	Journal	Published Year	Pages	File Type
8536862	Pharmacology & Therapeutics	2018	29 Pages	PDF

Abstract

Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15Â months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.

Keywords

AMPK CSC EGFR HMGA2 ALDH MMP EGF MDR Jnk GTP CMA KRAS CX43 bFGF APE CD44 Mcl-1 Bcl-2 ERK IFN-β HDAC BFP MGMT BER CaMKII JAK2 BMF ATG LC3 CBP ATF6 DISC FADD GSK3β DRD4 Bcl-xL DRP ACD HIF ABCB1 ATRX MMR GSC BRAF MLH1 GLI1 IDH HCQ v-raf murine sarcoma viral oncogene homolog B1 MDR1 EZH2 IRE Janus Kinase 2 metabotropic glutamate receptor 3 IL-24 Fas-L MPG CDKN2A/B MSH ABCG FAM134B DRAM ATP-binding cassette sub-family B member 1 Bcl-2 homologous antagonist/killer Methylguanine-DNA methyltransferase GIC MicroRNA-9 GNS ID4 Mitogen-activated kinases GANT61 FEN1 mGluR3 Dll3 Delta-like 3 Dopamine receptor 4 GRPs Jun amino-terminal kinases BCL-2 related ovarian killer MTIC AMP-activated protein kinase apurinic/apyrimidinic apurinic/apyrimidinic endonuclease Chaperone-mediated autophagy Bmi1 C/EBP homologous protein c-Myb guanosine-5′-triphosphate Myeloid cell leukemia-1 LIG MAPK Mda-7 MiR-9 MutL homolog 1 Adenosine Triphosphate ATP aldehyde dehydrogenase Akt epithelial mesenchymal transition Isocitrate dehydrogenase Interferon-β Interleukin-24 Bax LIR BIK mismatch repair base excision repair enhancer of zeste homolog 2 EMT CHOP c-Jun Fas-associated death domain cluster of differentiation 44 CNS electron transport chain glioma stem cell cancer stem cell central nervous system extracellular signal regulated kinase endoplasmic reticulum epidermal growth factor Fas Ligand Hypoxia-inducible factor basic fibroblast growth factor activating transcription factor 6 Flap endonuclease 1 LAMP B-cell lymphoma-2 Ligase Matrix metalloproteinases BIM BMP Autophagic cell death cyclin-dependent kinase inhibitor 2A Homologous recombination Bcl-2 homology Melanocyte-stimulating hormone hydroxychloroquine histone deacetylase ETc calmodulin-dependent protein kinase II Bcl-2 Associated X protein CREB-binding protein Lysosomal membrane protein multidrug resistance protein 1 Bone morphogenetic protein BAK BID autophagy-related gene Bok Kirsten Rat Sarcoma Chloroquine connexin-43 Glioblastoma Glycogen synthase kinase 3β Epidermal growth factor receptor