A view on drug resistance in cancer.
A view on drug resistance in cancer.
复制标题
DOI：
10.1038/s41586-019-1730-1
复制
发表时间：
2019-11
期刊：
影响因子：
64.8
通讯作者：
Hyman DM
中科院分区：
文献类型：
--
作者：
Vasan N;Baselga J;Hyman DM
癌症治疗的耐药性问题是多方面的。在这里，我们采取还原论的方法来定义和分离耐药性的关键决定因素，其中包括肿瘤负荷和生长动力学;肿瘤异质性;物理屏障;免疫系统和微环境;不可治愈的癌症驱动因素;以及施加治疗压力的许多后果。我们提出了四种耐药性的一般解决方案，这些解决方案基于早期检测肿瘤，允许癌症拦截;治疗期间的自适应监测;添加新药和改进的药理学原理，导致更深层次的反应;以及通过高通量合成致死性筛选，整合临床基因组数据和计算建模来识别癌细胞依赖性。这些不同的方法最终可以在任何决策点针对每个肿瘤进行综合，并用于指导治疗的选择。
The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.
登录
查看更多内容
影响因子：
10.9
作者：
Anderson ES;Postow MA;Wolchok JD;Young RJ;Ballangrud Å;Chan TA;Yamada Y;Beal K
通讯作者：
Beal K
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C
影响因子：
64.8
作者：
Burr ML;Sparbier CE;Chan YC;Williamson JC;Woods K;Beavis PA;Lam EYN;Henderson MA;Bell CC;Stolzenburg S;Gilan O;Bloor S;Noori T;Morgens DW;Bassik MC;Neeson PJ;Behren A;Darcy PK;Dawson SJ;Voskoboinik I;Trapani JA;Cebon J;Lehner PJ;Dawson MA
通讯作者：
Dawson MA
影响因子：
78.8
作者：
Abbosh, Christopher;Birkbak, Nicolai J.;Swanton, Charles
通讯作者：
Swanton, Charles
影响因子：
168.9
作者：
Boddington, C.;Bradley, R.;Zambetti, M.
通讯作者：
Zambetti, M.