Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies
Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies
复制标题
CDK4/6 抑制剂的内在和获得性耐药性以及潜在的克服策略
DOI：
10.1038/s41401-020-0416-4
复制
发表时间：
2020-06
影响因子：
8.2
通讯作者：
Ding Ling
中科院分区：
文献类型：
--
作者：
Xu Xia-qing;Pan Xiao-hui;Wang Ting-ting;Wang Jian;Yang Bo;He Qiao-jun;Ding Ling
细胞周期蛋白依赖性激酶（cyclin-dependent kinases，CDKs）的异常激活导致细胞异常增殖是肿瘤的固有特征之一。因此，靶向CDK的活性代表了一种有前途的肿瘤治疗策略。目前，靶向CDK 4和CDK 6的特异性抑制剂已被批准与内分泌治疗联合用于治疗雌激素受体阳性、人表皮生长因子受体2阴性（ER+ HER 2 −）乳腺癌;其他联合策略正在许多临床试验中进行测试。然而，对CDK 4/6抑制剂的获得性耐药性已经出现。由于细胞周期是由一系列生物学事件协调的，调节细胞周期进程的其他分子事件的改变可能涉及对CDK 4/6抑制剂的内在抗性。本文主要讨论CDK 4/6抑制剂的内在耐药和获得性耐药的机制，以及CDK 4/6抑制剂与其他信号通路抑制剂的联合用药策略，以期扩大CDK 4/6抑制剂在肿瘤治疗中的应用。
Abnormal activation of the cyclin-dependent kinases (CDKs), which result in aberrant cell proliferation, is one of the inherent characteristics of tumor. Thus targeting the activity of CDKs represents a promising tumor therapeutic strategy. Currently, the specific inhibitors that target CDK4 and CDK6 have been approved for the treatment of estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+HER2−) breast cancer in combination with endocrine therapy; other combination strategies are being tested in a number of clinical trials. However, the acquired resistance to CDK4/6 inhibitors has emerged. As the cell cycle is orchestrated by a series of biological events, the alterations of other molecular events that regulate the cell cycle progression may be involved in intrinsic resistance to CDK4/6 inhibitors. In this review we mainly discuss the mechanisms underlying intrinsic resistance and acquired resistance to CDK4/6 inhibitors as well as combination strategies with other signal pathway inhibitors being tested in clinical and pre-clinical studies, to extend the use of CDK4/6 inhibitors in tumor treatment.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-14-2955
发表时间：
2015-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Olanich ME;Sun W;Hewitt SM;Abdullaev Z;Pack SD;Barr FG
通讯作者：
Barr FG
DOI：
10.1186/s13058-016-0766-5
发表时间：
2016-11-08
期刊：
Breast Cancer Research : BCR
影响因子：
--
作者：
Azmil AM;Bansal GJ;Davies E;Wallis M;Kilburn-Toppin F;Taylor-Phillip S;Buckley A;Healy N;Quinn A;O’Keeffe S;Ang T;Maxwell A;Lim YY;Harkness E;Emsley R;Astley S;Gadde S;Ang T;Maxwell A;Lim YY;Harkness E;Emsley R;Astley S;Gadde S;Ferguson J;Stevens G;Hills R;Thomas KG;Rajan S;Sharma N;Kishore A;O’ Dowd J;Murphy C;Lindsay K;Dadayal G;Moody AN;Whitaker M;Wolstenhulme S;Bull J;Sharma N;Culpan AM;Roszkowski N;Grima A;Stahnke M;Rubin C;Walker R;Oeppen R;Puttagunta S;Gray K;Puri S;Sharma N;Millican-Slater R;Pascaline S;Hajaj M;Flinn J;Thomson K;Elsberger B;Turnbull A;Bagnall M;York J;Benney S;Goyal A;Topps A;Barr S;Pikoulas P;Pritchard S;Maxwell A;Greenhalgh S;Sreenivas M;Greenhalgh S;Sreenivas M;Greenhalgh S;Sreenivas M;Nandhra A;Sharma S;Gulati A;Razzaq F;Khan S;McKillen J;Larkin R;Sreenivas M;Kamat S;Goncalves C;Tan A;Eleti A;Vidyaprakash N;McMahon MA;Dall BJ;Sharma N;Majid F;Sreenivas M;Rattehalli R;Gaur V;Mackenzie A;Warren L;Patel M;Halling-Brown M;Wilkinson L;Young K;Tanner J;Wallis M;Currie R;Balyes S;Wragg J;Zamfir G;Ayra P;Marsden M;Butterworth J;Sinha S;Desai A;Metafa A;Whitaker M;Nielsen-Moody A;Wolstenhulme S;Sharma N;Bull J;Ward L;Heller S;Hudson S;Wilkinson L;Taylor K;Xyda A;Turnbull A;Allen S;Orlowski E;York J;Downey K;Sidebottom R;Wallis M;Lodhi A;Harkness E;Maxwell A;Howell A;Evans G;Gadde S;Astley S;Lim Y;Chen Y;Lepine-Williams E;Henderson S;Litherland J;Altaf N;Bury Y;Forester N;Chin MC;Litherland J;Taylor C;Skippage P;Sian A;McAvinchey R;Evans T;Stevens G;Nisbet S;Murray A;Thomas KG;Castillo RC;Markham H;Oeppen R;Thomas T;Jain A;Molderson J;Wan J;Newman H;Lowes S;Lunt L;Sultana S;Chillal V;Sreenivas M;Dalton R;Reeves D;Sergeant J;Harkness E;Gadde S;Maxwell A;Lim Y;Astley S;Edwards L;Jenkins K;Stevens G;Jain A;Molderson J;Shaikh S;Sidebottom R;O’Flynn E;Bombroffe L;Hughes J;Scurr E;Wilson R;Jones L;Govindarajulu S;Sahu AK;Brown M;Allen S;O’Flynn L;deSouza N;Rahim R;Wasan R;Goligher J;Wijesuriya S;Morel J;Peacock C;Michell M;Iqbal A;Evans D;Batohi B;Wasan T;Phillips V;Manuel E;Bowman G;Satchithananda K;Batohi B;Fang C;Michell M;Morel J;Shah C;Wijesuriya S;Peacock C;Rahim R;Wasan R;Goligher J;Satchithananda K;Altaf N;Forester N;Hodkin L;Horgan K;Dodwell D;Sharma N;Moloney B;Casey MC;Breathnach A;Dwyer RM;McLoughlin R;Sweeney KJ;Malone C;Healy MJ;Kerin MJ;Forester N;Lowes S;Mitchell E;Twiddy M;Maxwell A;Sharma N;Dobson H;Vinnicombe S;Evans A;Grant D;Bishop B;Giggens R;Bhuva S;Royds J;Camilleri F;Babu G;Beveridge C;Geach R;Klimczak K;Massey H;Lyburn I;Wan J;Jain A;Molderson J;Salehi-Bird S;Nishtala S;Gunning L;Changaradil DV;Bansal J;Davis J;Sharma A;Del Voscovo E;Etheridge H;Butler A;Fenne DS;Rubin G;Burt H;Ridley N;Taylor S;Sreenivas M;Seth S;Seth A
通讯作者：
Seth A
DOI：
10.1158/1078-0432.ccr-18-0410
发表时间：
2018-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
de Leeuw R;McNair C;Schiewer MJ;Neupane NP;Brand LJ;Augello MA;Li Z;Cheng LC;Yoshida A;Courtney SM;Hazard ES;Hardiman G;Hussain MH;Diehl JA;Drake JM;Kelly WK;Knudsen KE
通讯作者：
Knudsen KE
影响因子：
3.8
作者：
Monferrer, Ezequiel;Burgos-Panadero, Rebeca;Noguera, Rosa
通讯作者：
Noguera, Rosa