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DOI | 10.1038/s41467-019-10006-5 |
Spatial competition constrains resistance to targeted cancer therapy | |
Bacevic, Katarina1; Noble, Robert2,5; Soffar, Ahmed1,6; Ammar, Orchid Wael1; Boszonyik, Benjamin1; Prieto, Susana1; Vincent, Charles3; Hochberg, Michael E.2,4; Krasinska, Liliana1; Fisher, Daniel1 | |
2019-05-23 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | France; USA; Switzerland; Egypt |
英文摘要 | Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden and resistance in tumour spheroids, but not in monolayer culture. Mathematical modelling indicates that tumour spatial structure amplifies the fitness penalty of resistant cells, and identifies their relative fitness as a critical determinant of the clinical benefit of AT. Our results justify further investigation of AT with kinase inhibitors. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417467100005 |
WOS关键词 | KINASE INHIBITORS ; BREAST-CANCER ; TUMOR-GROWTH ; METRONOMIC CHEMOTHERAPY ; CDK4/6 INHIBITION ; DRUG-RESISTANCE ; CELL-DIVISION ; CDK2 ; EVOLUTION ; PROLIFERATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204381 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Montpellier, CNRS, IGMM, F-34090 Montpellier, France; 2.Univ Montpellier, ISEM, F-34090 Montpellier, France; 3.INSERM, IRCM, F-34090 Montpellier, France; 4.Santa Fe Inst, Santa Fe, NM 87501 USA; 5.Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland; 6.Alexandria Univ, Div Mol Biol, Fac Sci, Dept Zool, Alexandria 21526, Egypt |
推荐引用方式 GB/T 7714 | Bacevic, Katarina,Noble, Robert,Soffar, Ahmed,et al. Spatial competition constrains resistance to targeted cancer therapy[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Bacevic, Katarina.,Noble, Robert.,Soffar, Ahmed.,Ammar, Orchid Wael.,Boszonyik, Benjamin.,...&Fisher, Daniel.(2019).Spatial competition constrains resistance to targeted cancer therapy.NATURE COMMUNICATIONS,8. |
MLA | Bacevic, Katarina,et al."Spatial competition constrains resistance to targeted cancer therapy".NATURE COMMUNICATIONS 8(2019). |
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