基于PyMQ构建的PKM2蛋白结构，图片来自维基共享资源。
根据2012年1月23日在线发表在Journal of Experimental Medicine期刊上的一项研究，当氧气稀缺时，破坏一种允许癌细胞生长的蛋白能够导致肿瘤退化。
在癌细胞中，一种称作PKM2(丙酮酸激酶M2异构体)的酶大量产生，从而允许它们在肿瘤内部发现的严峻低氧环境中产生能量。
美国麻省理工学院的Michael Goldberg和Phillip Sharp如今发现抑制PKM2能够剥夺癌细胞的能量从而杀死它们，但是让正常细胞毫发无损。破坏PKM2导致小鼠中建立的肿瘤消失。如果这些结果在人类中仍然正确的话，这种策略可能提供一种有效的对抗很多种癌症类型的方法，同时使得产生的副作用最小化。(生物谷：towersimper编译)
doi:10.1084/jem.20111487
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Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Michael S. Goldberg and Phillip A. Sharp
The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.
