Targeting the absence and therapeutic engineering for cancer therapy

被引:38
作者
Blagosklonny, Mikhail V. [1 ]
机构
[1] Ordway Res Inst, Albany, NY USA
[2] Oncotarget Inc, Albany, NY USA
关键词
cancer; chemotherapy; targets; cure; drug resistance; drug combinations;
D O I
10.4161/cc.7.10.6250
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The Gotham Prize was awarded to Alex Varshavsky for "Targeting the absence", a strategy employing negative targets of cancer therapy. This is a brilliant example of therapeutic engineering: designing a sequence of events that leads to the selective killing of one type of cell, while sparing all others. A complex molecular device ( Varshavsky's Demon) examines DNA, recognizes the present target in normal cells and kills cancer cells. The strategy is limited by the delivery ( transfection or infection) of DNA-based devices into each cell of our body. How can we overcome this limitation? Can therapeutic engineering be applied to small drugs? Can each small molecule reach a cell separately and, once in a cell, exert orchestrated action governed by cellular context? Here I describe how a combination of small drugs can acquire a demonic power to check, choose and selectively kill. The cytotoxicity is restricted to cells lacking ( or having) one of the targets. For example, in the presence of a normal target, one drug can cancel the cytotoxic action of another drug. And by increasing a number of targets, we can increase the precision and power of such 'restrictive' combinations. Here I discuss restrictive combinations of currently available drugs that could be tested in clinical trials. Could then these combinations cure cancer today? And what does 'cure' really mean? This article suggests the answer.
引用
收藏
页码:1307 / 1312
页数:6
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