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使 MYC 向癌细胞死亡倾斜。

Tilting MYC toward cancer cell death.

机构信息

Division of Cancer Pathobiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Division of Cancer Pathobiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

出版信息

Trends Cancer. 2021 Nov;7(11):982-994. doi: 10.1016/j.trecan.2021.08.002. Epub 2021 Sep 2.

Abstract

MYC oncoprotein promotes cell proliferation and serves as the key driver in many human cancers; therefore, considerable effort has been expended to develop reliable pharmacological methods to suppress its expression or function. Despite impressive progress, MYC-targeting drugs have not reached the clinic. Recent advances suggest that within a limited expression range unique to each tumor, MYC oncoprotein can have a paradoxical, proapoptotic function. Here we introduce a counterintuitive idea that modestly and transiently elevating MYC levels could aid chemotherapy-induced apoptosis and thus benefit the patients as much, if not more than MYC inhibition.

摘要

MYC 癌蛋白促进细胞增殖,是许多人类癌症的关键驱动因子;因此,人们付出了相当大的努力来开发可靠的药理学方法来抑制其表达或功能。尽管取得了令人印象深刻的进展,但 MYC 靶向药物尚未进入临床。最近的进展表明,在每个肿瘤特有的有限表达范围内,MYC 癌蛋白可以具有矛盾的促凋亡功能。在这里,我们提出了一个违反直觉的想法,即适度和短暂地提高 MYC 水平可以帮助化疗诱导的细胞凋亡,从而使患者受益,即使不比 MYC 抑制更多。

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引用本文的文献

本文引用的文献

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Nat Cancer. 2020 Aug;1(8):774-783. doi: 10.1038/s43018-020-0100-0. Epub 2020 Aug 10.
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Capitalizing on Synthetic Lethality of MYC to Treat Cancer in the Digital Age.利用 MYC 的合成致死性在数字时代治疗癌症。
Trends Pharmacol Sci. 2021 Mar;42(3):166-182. doi: 10.1016/j.tips.2020.11.014. Epub 2021 Jan 6.
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Turning Up the Heat on MYC: Progress in Small-Molecule Inhibitors.调高 MYC 的温度:小分子抑制剂的进展。
Cancer Res. 2021 Jan 15;81(2):248-253. doi: 10.1158/0008-5472.CAN-20-2959. Epub 2020 Oct 21.
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