Cancer nuclear envelope rupture and repair in taxane resistance  

作　　者：Ana P.Xu Lucy B.Xu Elizabeth R.Smith Joshua S.Fleishman Zhe-Sheng Chen Xiang-Xi Xu 

机构地区：[1]University of Miami,Miami,FL,USA [2]Sylvester Comprehensive Cancer Center,University of Miami Miller School of Medicine,Miami,FL 33136,USA [3]Department of Obstetrics,Gynecology and Reproductive Science,University of Miami Miller School of Medicine,Miami,FL,USA [4]College of Pharmacy and Health Sciences,St.John’s University,Queens New York,USA [5]Department of Radiation Oncology,University of Miami Miller School of Medicine,Miami,FL 33136,USA

出　　处：《Medical Review》2024年第6期522-530,共9页医学评论(英文)

基　　金：partially supported by NIH funding R01 CA095071,CA79716,and CA75389 to XX from NCI,NIH;seed funding from Sylvester Comprehensive Cancer Center,University of Miami.

摘　　要：Taxanes,including paclitaxel,docetaxel,and cabazitaxel,are key agents in cancer treatment,often used as frontline chemotherapy drugs in combination with other agent(s)(commonly carboplatin)and as second-line treatments alone.Generally,taxanes are highly effective,but drug resistance unavoidably develops following repeated treatment.Taxanes work by binding to and stabilizing microtubules,leading to mitotic arrest,mitotic catastrophe,and micronucleation.The long-recognized mechanisms of drug resistance generally can be classified into three categories:drug efflux,microtubule polymerization,and apoptotic pathway.A recent new addition to this list is a mechanism related to the nuclear envelope,as cancer cells undergo micronucleation and nuclear membrane rupture when treated with taxanes.All these mechanismsmay operate simultaneously as taxane resistance is multi-factorial.Here,we review the cell biology understanding of nuclear envelope breaking in production of micronucleation,and nuclear membrane rupture and repair,and propose that these processes are involved in taxane resistance.

关 键 词：chemotherapy drug resistance TAXANES PACLITAXEL MICROTUBULES nuclear envelope 

分 类 号：R73[医药卫生—肿瘤]