Weizmann Institute of Science, Rehovot, Israel.
Weizmann Institute of Science, Rehovot, Israel.
Semin Cancer Biol. 2019 Dec;59:36-49. doi: 10.1016/j.semcancer.2019.02.002. Epub 2019 Feb 10.
Almost thirty years ago, PI3K was discovered as a lipid kinase associated with certain oncoproteins. The first decade of research on PI3K saw the identification, purification and cloning of PI3Kα. The second decade of research was noted for the identification of some of PI3K's activators and effectors. This was accompanied by the discovery that PI3K acts as a retroviral oncogene. The third decade was known for the establishment of the direct involvement of PI3K in cancer, demonstrated by the identification of cancer-specific mutations. Efforts to target PI3K were on the rise from that moment on, accompanied by the first clinical trials for PI3K inhibitor therapies. In the fourth decade of research, PI3K-based cancer drugs will continue to emerge, as will new knowledge regarding other uncovered functions of this protein and pathway.
大约三十年前，PI3K 作为一种与某些癌蛋白相关的脂质激酶被发现。PI3K 研究的第一个十年见证了 PI3Kα 的鉴定、纯化和克隆。研究的第二个十年以确定一些 PI3K 的激活剂和效应物为特点。同时发现 PI3K 作为逆转录病毒致癌基因发挥作用。研究的第三个十年以确定 PI3K 直接参与癌症为标志，这是通过鉴定癌症特异性突变来证明的。从那时起，针对 PI3K 的靶向治疗方法不断涌现，同时也进行了第一批针对 PI3K 抑制剂治疗的临床试验。在研究的第四个十年中，基于 PI3K 的癌症药物将继续出现，同时也将有更多关于该蛋白和途径未被发现的其他功能的新知识。
