The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy;these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after in...The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy;these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies.Compelling evidence suggests that cancer stem cells(CSCs)have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation,relapse,metastasis,and chemo-resistance.Thus,a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates.In this review,the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors.We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs.This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers,regulating CSC-associated oncogenes and signaling pathways,inhibiting drug-efflux pumps involved in drug resistance,modulating the tumor microenvironment and immune system,and applying drug combination therapy using nanomedicine.展开更多
基金supported by National Institutes of Health grants(R01AI068978,R01CA170820 and P01CA132681)a translational acceleration grant from the Joint Center for Translational Medicine,the National Cancer Institute(P30CA014089)a grant from the Ming Hsieh Institute for Research on Engineering Medicine for Cancer.
文摘The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy;these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies.Compelling evidence suggests that cancer stem cells(CSCs)have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation,relapse,metastasis,and chemo-resistance.Thus,a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates.In this review,the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors.We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs.This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers,regulating CSC-associated oncogenes and signaling pathways,inhibiting drug-efflux pumps involved in drug resistance,modulating the tumor microenvironment and immune system,and applying drug combination therapy using nanomedicine.