Cancer cell heterogeneity & plasticity in glioblastoma and brain tumors. (July 2022)

• Record Type: Journal Article
• Authors: Lauko, Adam; Lo, Alice; Ahluwalia, Manmeet S.; Lathia, Justin D.
• Is Part Of: Seminars in cancer biology. Volume 82(2022)
• Page Start: 162
• Page End: 175
• Publication Date: 2022-07
• Subjects: CNS Central nervous system -- GBM glioblastoma -- DIPG diffuse intrinsic pontine glioma -- WHO World Health Organization -- TMZ temozolomide -- TTF tumor-treating fields -- CSCs cancer stem cells -- WGA whole genome amplification -- EGFR epidermal growth factor receptor -- IDH1 isocitrate dehydrogenase -- MDM murine double minute -- TERT telomerase reverse transcriptase -- PDGFRA platelet-derived growth factor receptor alpha -- PTEN phosphatase and tensin homolog -- ATRX ATRX chromatin remodeler -- PIK3CA phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha -- CDK4 cyclin-dependent kinase 4 -- TCGA The Cancer Genome Atlas -- CAN copy number alteration -- Ivy GAP IVY Glioblastoma Atlas Project -- NPC neural-progenitor cell -- OPC oligodendrocyte progenitor cell -- AC astrocyte -- G-CIMP glioma-CpG island methylator phenotype -- N6-ma N6-methyladenine -- m6A N6-methyladenosine -- ALKBH1 AlkB homolog 1, histone H2A dioxygenase -- HIFs hypoxia-inducible factors -- VEGF vascular endothelial growth factor -- TME tumor microenvironment -- SDF-1 stromal derived factor-1 -- TGF-β transforming growth factor-β -- FGF2 fibroblastic growth factor 2 -- NLGN3 neuroligin-3 -- NMDARs N-methyl-D-aspartate receptors -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- RANKL receptor activator of nuclear factor kappa-B ligand -- GDF-15 growth/differentiation factor 15 -- CTGF connective tissue growth factor -- TAMs tumor-associated macrophages -- TILs tumor-infiltrating lymphocytes -- MIF macrophage migration inhibitory factor -- MDSCs myeloid-derived suppressor cells -- mMDSCs monocytic MDSCs -- mMDSCs granulocytic MDSCs -- CSF-1R colony-stimulating factor-1R -- JAM-A junctional adhesion molecule-A; Glioblastoma -- Heterogeneity -- Plasticity -- Epigenetics -- Tumor microenvironment; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2021.02.014
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Brain tumors remain one of the most difficult tumors to treat and, depending on the diagnosis, have a poor prognosis. Of brain tumors, glioblastoma (GBM) is the most common malignant glioma and has a dismal prognosis, with only about 5% of patients alive five years after diagnosis. While advances in targeted therapies and immunotherapies are rapidly improving outcomes in a variety of other cancers, the standard of care for GBM has largely remained unaltered since 2005. There are many well-studied challenges that are either unique to brain tumors (i.e., blood-brain barrier and immunosuppressive environment) or amplified within GBM (i.e., tumor heterogeneity at the cellular and molecular levels, plasticity, and cancer stem cells) that make this disease particularly difficult to treat. While we touch on all these concepts, the focus of this review is to discuss the immense inter- and intra-tumoral heterogeneity and advances in our understanding of tumor cell plasticity and epigenetics in GBM. With each improvement in technology, our understanding of the complexity of tumoral heterogeneity and plasticity improves and we gain more clarity on the causes underlying previous therapeutic failures. However, these advances are unlocking new therapeutic opportunities that scientists and physicians are currently exploiting and have the potential for new breakthroughs.