期刊
CHEMISTRY & BIOLOGY
卷 22, 期 8, 页码 1144-1155出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2015.06.021
关键词
-
资金
- Academy of Finland [269 862, 272 437, 277 293, 279 163]
- Helsinki Biomedical Graduate Program (HBGP)
- Cancer Society of Finland
- Biomedicum Helsinki Foundation
- Biocenter Finland
- Jane and Aatos Erkko Foundation
- Cancer Foundation Finland sr [140087] Funding Source: researchfish
Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据