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