Cancer stem cell theory: therapeutic implications for nanomedicine

Abstract

Ke Wang,1 Xianguo Wu,2 Jianwei Wang,3 Jian Huang1,31Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), 2Department of Clinical Laboratory, 3Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of ChinaAbstract: Evidence continues to accumulate showing that tumors contain a minority population of cells responsible for tumor initiation, growth, and recurrence. These are termed "cancer stem cells" (CSCs). Functional assays have identified the self-renewal and tumor-initiation capabilities of CSCs. Moreover, recent studies have revealed that these CSCs is responsible for chemotherapy resistance within a tumor. Several mechanisms of chemoresistance have been proposed, including increased Wnt/β-catenin and Notch signaling, as well as high expression levels of adenosine triphosphate-binding cassette transporters, an active DNA repair capacity, and slow rate of self-renewal. Nanoscale drug-delivery systems, which transport therapeutically active molecules, prolong circulation, and improve biodistribution in the body, may allow more effective and specific therapies to address the challenges posed by CSCs. In particular, some nanovehicles are being exploited for selective drug delivery to CSCs and show promising results. In this review, we highlight the mechanisms of drug resistance and the novel strategies using nanoscale drugs to eliminate CSCs.Keywords: drug resistance, drug delivery, chemoresistance, Wnt/β-catenin signaling, Notch signaling