通过靶向BET溴结构域对拉帕替尼的适应性旁路反应进行表观遗传抑制。
Epigenetic inhibition of adaptive bypass responses to lapatinib by targeting BET Bromodomains.
作者信息
Stuhlmiller Timothy J, Miller Samantha M, Johnson Gary L
机构信息
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine , Chapel Hill, NC, USA.
出版信息
Mol Cell Oncol. 2015 Jun 10;3(1):e1052182. doi: 10.1080/23723556.2015.1052182. eCollection 2016 Jan.
Abstract
The characterization of kinases as oncogenic drivers has led to more than 30 FDA-approved targeted kinase inhibitors for cancer treatment. Unfortunately, these therapeutics fail to have clinical durability because of adaptive responses from the kinome and transcriptome that bypass inhibition of the targeted pathway. In our recent work, we describe a method to prevent these adaptive responses at an epigenetic level, generating a durable response to kinase inhibition.
摘要
激酶作为致癌驱动因子的特性已促使超过30种经美国食品药品监督管理局批准的靶向激酶抑制剂用于癌症治疗。不幸的是，由于激酶组和转录组的适应性反应绕过了对靶向通路的抑制，这些疗法未能产生持久的临床疗效。在我们最近的工作中，我们描述了一种在表观遗传水平上预防这些适应性反应的方法，从而产生对激酶抑制的持久反应。
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本文引用的文献
1
Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains.
Cell Rep. 2015 Apr 21;11(3):390-404. doi: 10.1016/j.celrep.2015.03.037. Epub 2015 Apr 9.
2
Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma.
Nature. 2014 Apr 3;508(7494):118-22. doi: 10.1038/nature13121. Epub 2014 Mar 26.
3
Bypass mechanisms of resistance to receptor tyrosine kinase inhibition in lung cancer.
Sci Signal. 2013 Sep 24;6(294):re6. doi: 10.1126/scisignal.2004652.
4
A receptor tyrosine kinase network composed of fibroblast growth factor receptors, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, and hepatocyte growth factor receptor drives growth and survival of head and neck squamous carcinoma cell lines.
Mol Pharmacol. 2013 Apr;83(4):882-93. doi: 10.1124/mol.112.084111. Epub 2013 Jan 31.
5
Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer.
Cell. 2012 Apr 13;149(2):307-21. doi: 10.1016/j.cell.2012.02.053.
6
Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition.
Oncogene. 2011 Oct 6;30(40):4163-74. doi: 10.1038/onc.2011.130. Epub 2011 Apr 18.
7
Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways.
Nat Med. 2011 Apr;17(4):461-9. doi: 10.1038/nm.2309. Epub 2011 Mar 13.
8
Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase.
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5021-6. doi: 10.1073/pnas.1016140108. Epub 2011 Mar 8.
9
AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity.
Cancer Cell. 2011 Jan 18;19(1):58-71. doi: 10.1016/j.ccr.2010.10.031. Epub 2011 Jan 6.
10
Resiliency and vulnerability in the HER2-HER3 tumorigenic driver.
Sci Transl Med. 2010 Jan 27;2(16):16ra7. doi: 10.1126/scitranslmed.3000389.
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