A Convergence-Based Framework for Cancer Drug Resistance.
A Convergence-Based Framework for Cancer Drug Resistance.
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DOI：
10.1016/j.ccell.2018.03.025
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发表时间：
2018-05-14
期刊：
影响因子：
50.3
通讯作者：
Garraway LA
中科院分区：
文献类型：
--
作者：
Konieczkowski DJ;Johannessen CM;Garraway LA
尽管癌症生物学和治疗学取得了进步，但耐药性仍然是个问题。阻力通常是多因素的、异质的，并且容易出现采样不足的情况。尽管如此，靶向治疗抵抗的许多个体机制可能会合并成较少数量的收敛，包括通路重新激活（原始效应器的下游重新接合）、通路旁路（招募收敛于相同下游输出的平行通路）和通路冷漠（独立于初始治疗目标的细胞状态的发展）。类似的趋同也可能是免疫治疗耐药性的基础。这种简约的、基于收敛的框架可能有助于解释跨肿瘤类型和治疗类别的耐药性，也可能提出克服耐药性的策略。
Despite advances in cancer biology and therapeutics, drug resistance remains problematic. Resistance is often multifactorial, heterogeneous, and prone to undersampling. Nonetheless, many individual mechanisms of targeted therapy resistance may coalesce into a smaller number of convergences, including pathway reactivation (downstream re-engagement of original effectors), pathway bypass (recruitment of a parallel pathway converging on the same downstream output), and pathway indifference (development of a cellular state independent of the initial therapeutic target). Similar convergences may also underpin immunotherapy resistance. Such parsimonious, convergence-based frameworks may help explain resistance across tumor types and therapeutic categories and may also suggest strategies to overcome it.
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影响因子：
17.1
作者：
Chmielecki J;Foo J;Oxnard GR;Hutchinson K;Ohashi K;Somwar R;Wang L;Amato KR;Arcila M;Sos ML;Socci ND;Viale A;de Stanchina E;Ginsberg MS;Thomas RK;Kris MG;Inoue A;Ladanyi M;Miller VA;Michor F;Pao W
通讯作者：
Pao W
影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
7.7
作者：
Balbas MD;Evans MJ;Hosfield DJ;Wongvipat J;Arora VK;Watson PA;Chen Y;Greene GL;Shen Y;Sawyers CL
通讯作者：
Sawyers CL
影响因子：
28.2
作者：
Bardelli A;Corso S;Bertotti A;Hobor S;Valtorta E;Siravegna G;Sartore-Bianchi A;Scala E;Cassingena A;Zecchin D;Apicella M;Migliardi G;Galimi F;Lauricella C;Zanon C;Perera T;Veronese S;Corti G;Amatu A;Gambacorta M;Diaz LA Jr;Sausen M;Velculescu VE;Comoglio P;Trusolino L;Di Nicolantonio F;Giordano S;Siena S
通讯作者：
Siena S
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J