Despite the success of targeted therapies in cancer treatment,therapy-induced resistance remains a major obstacle to a completecure.Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic...Despite the success of targeted therapies in cancer treatment,therapy-induced resistance remains a major obstacle to a completecure.Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity.Severalreversible mechanisms have been proposed to circumvent tumor cell plasticity,including epigenetic modifications,regulation oftranscription factors,activation or suppression of key signaling pathways,as well as modification of the tumor environment.Epithelial-to-mesenchymal transition,tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity.Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employcombination treatments.In this review,we delineate the formation of tumor cell plasticity and its manipulation of tumor evasionfrom targeted therapy.We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types oftumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance.New therapeutic strategiessuch as inhibition or reversal of tumor cell plasticity are also presented.We also discuss the multitude of clinical trials that areongoing worldwide with the intention of improving clinical outcomes.These advances provide a direction for developing noveltherapeutic strategies and combination therapy regimens that target tumor cell plasticity.展开更多
基金the National Natural Science Foundation of China(12271467,81774089,82004110)the Jiangsu Province Key Research and Development Program(BE2020758,BE2019637)+5 种基金the Xuzhou Medical Outstanding Talents(Xuzhou Health Education Research[2017]No.22)the Jiangsu Medical Innovation Team(CXTDA2017048)the Key Projects of Xuzhou Science and Technology Plan(KC19075)the Xuzhou Clinical Medicine Expert Team Project(2018TD004)the Xuzhou Medical Key Talents Project(XWRCHT20220055)and the Xuzhou Medical Reserve Talents Project(XWRCHT20220009,XWRCHT20220012).
文摘Despite the success of targeted therapies in cancer treatment,therapy-induced resistance remains a major obstacle to a completecure.Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity.Severalreversible mechanisms have been proposed to circumvent tumor cell plasticity,including epigenetic modifications,regulation oftranscription factors,activation or suppression of key signaling pathways,as well as modification of the tumor environment.Epithelial-to-mesenchymal transition,tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity.Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employcombination treatments.In this review,we delineate the formation of tumor cell plasticity and its manipulation of tumor evasionfrom targeted therapy.We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types oftumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance.New therapeutic strategiessuch as inhibition or reversal of tumor cell plasticity are also presented.We also discuss the multitude of clinical trials that areongoing worldwide with the intention of improving clinical outcomes.These advances provide a direction for developing noveltherapeutic strategies and combination therapy regimens that target tumor cell plasticity.
