A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms. (April 2015)

• Record Type: Journal Article
• Authors: Cojoc, Monica; Mäbert, Katrin; Muders, Michael H.; Dubrovska, Anna
• Is Part Of: Seminars in cancer biology. Volume 31(2015)
• Page Start: 16
• Page End: 27
• Publication Date: 2015-04
• Subjects: ABCG2 ATP-binding cassette G2 -- ALDH aldehyde dehydrogenase -- ALK anaplastic lymphoma kinase -- AML acute myeloid leukemia -- ALL acute lymphoblastic leukemia -- APL acute promyelocytic leukemia -- ATM ataxia telangiectasia mutated protein kinase -- ATR ataxia telangiectasia and rad-3-related protein kinase -- ATRA all-trans retinoic acid -- BCRP breast cancer resistance protein -- BSO buthionine sulfoximine -- CAF cancer associated fibroblasts -- CCL2 chemokine (C-C motif) ligand 2 -- CD cluster of differentiation -- CHK1/2 checkpoint protein kinase 1 and 2 -- CSC cancer stem cell -- CXCL12 chemokine (C-X-C motif) ligand 12 -- CXCR4 (C-X-C) chemokine receptor type 4 -- DLL4 delta-like 4 ligand -- DNA-PK DNA-dependent protein kinase -- DSB double strand break -- ECM extracellular matrix -- EGF epidermal growth factor -- EMT epithelial–mesenchymal transition -- ERK extracellular-signal-regulated kinase -- FGF fibroblast growth factor -- GABA γ-amino butyric acid -- GSI gamma-secretase inhibitor -- GTN glyceryl-trinitrate -- HER2 human epidermal growth factor receptor 2 -- HIF hypoxia-inducible factor -- HNSCC head and neck squamous cell carcinoma -- HR homology-directed recombination -- IL interleukin -- KRAS Kirsten rat sarcoma -- MAPK mitogen-activated protein kinase -- MMP matrix metalloproteinase -- MRP1 multidrug resistance protein 1 -- MSC mesenchymal stem cell -- mTOR mammalian target of rapamycin -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NHEJ non-homologous end joining -- NRP2 neuropilin-2 -- NSCLC non-small cell lung cancer -- PDGF plateled derived growth factor -- PI3K phosphoinositide 3-kinase -- PIKK phosphatidylinositol 3-kinase-related kinase -- siRNA small interfering RNA -- SCLC small cell lung cancer -- SMAD small mothers against decapentaplegic -- SP side population -- STAT signal transducer and activator of transcription -- TGF-ß transforming growth factor β -- TMZ temozolomide -- TNBC triple-negative breast cancer -- TNFα tumor necrosis factor-alpha -- VEGF vascular endothelial growth factor -- WNT wingless-type MMTV integration site family; Cancer stem cells -- Therapy resistance -- Autophagy -- Hypoxia -- DNA repair; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2014.06.004
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Similar to normal tissue, many tumors have a hierarchical organization where tumorigenic cancer stem cells (CSCs) differentiate into non-tumorigenic progenies. A host of studies have demonstrated that although CSCs and their non-tumorigenic progenies within the same clone can share common genotype, they display different epigenetic profiles that results in changes of multiple signaling pathways. Many of these pathways confer cell adaptation to the microenvironmental stresses including inflammation, hypoxia, low pH, shortage in nutrients and anti-cancer therapies. Treatment strategies based on combination of conventional therapies targeting bulk tumor cells and CSC-specific pathway inhibition bear a promise to improve cancer cure compared to monotherapies. In this review we describe the mechanisms of CSC-related therapy resistance including drug efflux by ABC transporters, activation of aldehyde dehydrogenase and developmental pathways, enhanced DNA damage response, autophagy and microenvironmental conditions, and discuss possible therapeutic strategies for improving cancer treatment.