Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aav4474 |
Adaptive mutability of colorectal cancers in response to targeted therapies | |
Russo, Mariangela1,2; Crisafulli, Giovanni1,2; Sogari, Alberto1,2; Reilly, Nicole M.3; Arena, Sabrina1,2; Lamba, Simona1; Bartolini, Alice1; Amodio, Vito1,2; Magri, Alessandro1,2; Novara, Luca1; Sarotto, Ivana1; Nagel, Zachary D.4; Piett, Cortt G.4; Amatu, Alessio5,6; Sartore-Bianchi, Andrea5,6; Siena, Salvatore5,6; Bertotti, Andrea1,2; Trusolino, Livio1,2; Corigliano, Mattia7,8,9; Gherardi, Marco7,8,9; Lagomarsino, Marco Cosentino7,8,9; Di Nicolantonio, Federica1,2; Bardelli, Alberto1,2 | |
2019-12-20 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 366期号:6472页码:1473-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Italy; USA |
英文摘要 | The emergence of drug resistance limits the efficacy of targeted therapies in human tumors. The prevalent view is that resistance is a fait accompli: when treatment is initiated, cancers already contain drug-resistant mutant cells. Bacteria exposed to antibiotics transiently increase their mutation rates (adaptive mutability), thus improving the likelihood of survival. We investigated whether human colorectal cancer (CRC) cells likewise exploit adaptive mutability to evade therapeutic pressure. We found that epidermal growth factor receptor (EGFR)/BRAF inhibition down-regulates mismatch repair (MMR) and homologous recombination DNA-repair genes and concomitantly up-regulates error-prone polymerases in drug-tolerant (persister) cells. MMR proteins were also down-regulated in patient-derived xenografts and tumor specimens during therapy. EGFR/BRAF inhibition induced DNA damage, increased mutability, and triggered microsatellite instability. Thus, like unicellular organisms, tumor cells evade therapeutic pressures by enhancing mutability. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000503861000047 |
WOS关键词 | STRESS-INDUCED MUTAGENESIS ; PRONE DNA-POLYMERASES ; ANTI-EGFR THERAPY ; ACQUIRED-RESISTANCE ; DRUG-RESISTANCE ; REPAIR ; MUTATIONS ; BLOCKADE ; CELLS ; REPLICATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/226501 |
专题 | 环境与发展全球科技态势 |
作者单位 | 1.FPO IRCCS, Candiolo Canc Inst, I-10060 Candiolo, TO, Italy; 2.Univ Torino, Dept Oncol, I-10060 Candiolo, TO, Italy; 3.Fdn Piemontese Ric Canc ONLUS, I-10060 Candiolo, TO, Italy; 4.Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, JBL Ctr Radiat Sci, Boston, MA 02115 USA; 5.Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, I-20162 Milan, Italy; 6.Univ Milan, Dept Oncol & Hematooncol, I-20133 Milan, Italy; 7.IFOM FIRC Inst Mol Oncol, I-20139 Milan, Italy; 8.Univ Milan, Dept Phys, I-20133 Milan, Italy; 9.INFN, I-20133 Milan, Italy |
推荐引用方式 GB/T 7714 | Russo, Mariangela,Crisafulli, Giovanni,Sogari, Alberto,et al. Adaptive mutability of colorectal cancers in response to targeted therapies[J]. SCIENCE,2019,366(6472):1473-+. |
APA | Russo, Mariangela.,Crisafulli, Giovanni.,Sogari, Alberto.,Reilly, Nicole M..,Arena, Sabrina.,...&Bardelli, Alberto.(2019).Adaptive mutability of colorectal cancers in response to targeted therapies.SCIENCE,366(6472),1473-+. |
MLA | Russo, Mariangela,et al."Adaptive mutability of colorectal cancers in response to targeted therapies".SCIENCE 366.6472(2019):1473-+. |
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