Shenolikar Shirish
J Clin Invest. 2017 Jun 1;127(6):2048-2050. doi: 10.1172/JCI94763. Epub 2017 May 15.
Observed deficits in protein phosphatase 2A (PP2A) function in a variety of human cancers have stimulated drug discovery efforts aimed at restoring PP2A function to inhibit tumor growth. Work published by Sangodkar et al. in this issue of the JCI describes the characterization of orally available small molecule activators of PP2A (SMAPs). These SMAPs attenuated mitogenic signaling and triggered apoptosis in KRAS-mutant lung cancer cells and inhibited tumor growth in murine models. Tumors with mutations in the SMAP-binding site of the PP2A A subunit displayed resistance to SMAPs. Future studies that identify the PP2A-regulated events targeted by SMAPs should guide critical decisions about which cancers might be best treated with these molecules. This study provides encouraging evidence in favor of SMAPs as potential anticancer drugs.
在多种人类癌症中观察到的蛋白磷酸酶2A（PP2A）功能缺陷，激发了旨在恢复PP2A功能以抑制肿瘤生长的药物研发工作。桑戈德卡尔等人在本期《临床研究杂志》上发表的研究描述了PP2A口服小分子激活剂（SMAPs）的特性。这些SMAPs减弱了促有丝分裂信号传导，触发了KRAS突变肺癌细胞的凋亡，并在小鼠模型中抑制了肿瘤生长。PP2A A亚基的SMAP结合位点发生突变的肿瘤对SMAPs具有抗性。确定SMAPs靶向的PP2A调节事件的未来研究，应指导关于哪些癌症可能最适合用这些分子治疗的关键决策。这项研究为支持SMAPs作为潜在抗癌药物提供了令人鼓舞的证据。
