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AKT 抑制剂在癌症治疗中有未来吗？

Is There a Future for AKT Inhibitors in the Treatment of Cancer?

机构信息

Breast Cancer Program, Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University, Nashville, Tennessee.

出版信息

Clin Cancer Res. 2016 Jun 1;22(11):2599-601. doi: 10.1158/1078-0432.CCR-16-0100. Epub 2016 Mar 15.

DOI:10.1158/1078-0432.CCR-16-0100
PMID:26979397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4891224/
Abstract

An AKT inhibitor plus an antiestrogen exhibited no significant clinical activity in patients with ER(+)/HER2(-) breast cancer despite laboratory studies supporting an antitumor effect for both drugs combined. These results raise concerns about the development of AKT inhibitors in unselected patients whose tumors have unknown dependence on the PI3K/AKT pathway. Clin Cancer Res; 22(11); 2599-601. ©2016 AACRSee related article by Ma et al., p. 2650.

摘要

尽管实验室研究表明 AKT 抑制剂与抗雌激素药物联合应用具有抗肿瘤作用，但在 ER(+)/HER2(-) 乳腺癌患者中，联合用药并未显示出显著的临床活性。这些结果令人担忧的是，在那些肿瘤对 PI3K/AKT 通路的依赖性尚不清楚的未选择患者中开发 AKT 抑制剂的情况。临床癌症研究; 22(11); 2599-601. ©2016AACRSee 相关文章由 Ma 等人，第 2650 页。

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本文引用的文献

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A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer.AKT抑制剂MK-2206联合激素疗法用于雌激素受体阳性转移性乳腺癌绝经后女性的I期研究。
Clin Cancer Res. 2016 Jun 1;22(11):2650-8. doi: 10.1158/1078-0432.CCR-15-2160. Epub 2016 Jan 18.
2
A kinase-independent function of AKT promotes cancer cell survival.AKT的激酶非依赖性功能促进癌细胞存活。
Elife. 2014 Dec 31;3:e03751. doi: 10.7554/eLife.03751.
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PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting.癌症中的PI3K：异构体的不同作用、激活模式及治疗靶点
Nat Rev Cancer. 2015 Jan;15(1):7-24. doi: 10.1038/nrc3860.
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Molecular analysis for therapy choice: NCI MATCH.用于治疗选择的分子分析：美国国立癌症研究所（NCI）MATCH计划。
Semin Oncol. 2014 Jun;41(3):297-9. doi: 10.1053/j.seminoncol.2014.05.002. Epub 2014 May 22.
5
Autocrine IGF-I/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation.自分泌胰岛素样生长因子-I/胰岛素受体轴可补偿雌激素剥夺抗性的雌激素受体阳性乳腺癌细胞中AKT的抑制作用。
Breast Cancer Res. 2013;15(4):R55. doi: 10.1186/bcr3449.
6
Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers.PH-激酶结构域相互作用的破坏导致人类癌症中 AKT 的致癌激活。
Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19368-73. doi: 10.1073/pnas.1204384109. Epub 2012 Nov 7.
7
Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study.随机 II 期试验：依维莫司联合他莫昔芬治疗激素受体阳性、人表皮生长因子受体 2 阴性、既往接受过芳香化酶抑制剂治疗的转移性乳腺癌患者：GINECO 研究。
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PLoS One. 2010 Sep 23;5(9):e12913. doi: 10.1371/journal.pone.0012913.