Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces

作     者：Ahmad R.Safa 

作者机构：Department of Pharmacology and ToxicologyIndiana University School of MedicineIndianapolisIN 46202USA 

出 版 物：《Cancer Drug Resistance》 (癌症耐药（英文）)

年 卷 期：2022年第5卷第4期

页      面：850-872页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：U.S. Department of Defense, DOD, (OC 06095) National Cancer Institute, NCI, (CA 080734, CA 101743, CA 90878) 

主　　题：Cancer stem cells(CSCs) apoptosis drug resistance death receptor pathways anti-apoptotic proteins Bcl-2 family c-FLIP 

摘      要：Resistance to anticancer agents and apoptosis results in cancer relapse and is associated with cancer *** data have provided convincing evidence establishing that human cancers emerge from cancer stemcells (CSCs), which display self-renewal and are resistant to anticancer drugs, radiation, and apoptosis, andexpress enhanced epithelial to mesenchymal progression. CSCs represent a heterogeneous tumor cell populationand lack specific cellular targets, which makes it a great challenge to target and eradicate them. Similarly, theirclose relationship with the tumor microenvironment creates greater complexity in developing novel treatmentstrategies targeting CSCs. Several mechanisms participate in the drug and apoptosis resistance phenotype in CSCsin various cancers. These include enhanced expression of ATP-binding cassette membrane transporters, activationof various cytoprotective and survival signaling pathways, dysregulation of stemness signaling pathways, aberrantDNA repair mechanisms, increased quiescence, autophagy, increased immune evasion, deficiency ofmitochondrial-mediated apoptosis, upregulation of anti-apoptotic proteins including c-FLIP [cellular FLICE (FADDlikeIL-1β-converting enzyme)-inhibitory protein], Bcl-2 family members, inhibitors of apoptosis proteins, andPI3K/AKT signaling. Studying such mechanisms not only provides mechanistic insights into these cells that areunresponsive to drugs, but may lead to the development of targeted and effective therapeutics to eradicate *** studies have identified promising strategies to target CSCs. These emerging strategies may help targetCSC-associated drug resistance and metastasis in clinical settings. This article will review the CSCs drug and apoptosis resistance mechanisms and how to target CSCs.