A Convergence-Based Framework for Cancer Drug Resistance

被引：179

作者：

Konieczkowski, David J. ^{[1
]}

Johannessen, Cory M. ^{[2
]}

Garraway, Levi A. ^{[3
]}

机构：

[1] Harvard Radiat Oncol Program, Boston, MA 02114 USA

[2] Broad Inst, Cambridge, MA 02142 USA

[3] Eli Lilly & Co, Indianapolis, IN 46225 USA

来源：

CANCER CELL | 2018年 / 33卷 / 05期

关键词：

CELL LUNG-CANCER; METASTATIC BREAST-CANCER; NEUROENDOCRINE PROSTATE-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; BRAF INHIBITOR RESISTANCE; ANDROGEN-RECEPTOR GENE; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; TARGETED THERAPY; RAF INHIBITION;

D O I：

10.1016/j.ccell.2018.03.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：801 / 815

页数：15

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