Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The ...Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.展开更多
基金This work is supported by the National Key Scientific Program of China(2016YFA0100502)M.A.M.is a recipient of the CASTWAS President’s Fellowship.X.S.is a recipient of the 1000 Talents Plan Professorship for Young Talents(KJ2070000026).
文摘Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.
