Fruman David A, Chiu Honyin, Hopkins Benjamin D, Bagrodia Shubha, Cantley Lewis C, Abraham Robert T
Department of Molecular Biology & Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA.
Department of Molecular Biology & Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA.
Cell. 2017 Aug 10;170(4):605-635. doi: 10.1016/j.cell.2017.07.029.
Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases.
磷酸肌醇3-激酶（PI3K）的活性受到多种癌基因和生长因子受体的刺激，PI3K信号通路的增强被认为是癌症的一个标志。许多针对PI3K通路的疗法已在肿瘤学试验中进行了测试，一种亚型选择性抑制剂（idelalisib）已获得监管批准用于治疗某些血液癌症，还有多种其他药物正处于不同的研发阶段。与癌症生物学家对PI3K的研究并行的是，其他领域的研究发现了PI3K催化亚基和调节亚基在正常细胞功能和疾病中令人兴奋且常常出人意料的作用。其中许多功能通过影响PI3K靶向疗法的疗效和毒性对肿瘤学产生影响。在此，我们阐述I类PI3K在细胞代谢调节和免疫系统功能中的作用，这两个主题与癌症生物学紧密相关。我们还讨论了开发用于治疗癌症和其他疾病的PI3K靶向疗法的最新进展。
