Park Jin-Young, Lin Pei-yin, Weiss Robert H
Division of Nephrology, Department of Internal Medicine, Immunology Graduate Group, University of California, Davis, CA 95616, USA.
Expert Rev Anticancer Ther. 2007 Jun;7(6):863-70. doi: 10.1586/14737140.7.6.863.
Kidney cancer, or renal cell carcinoma, is a relatively rare malignancy but is metastatic at diagnosis in a third of patients; metastatic disease has a dismal prognosis. Conventional chemotherapy has been woefully inadequate, thus novel targets for 'designer' therapies are being actively evaluated. The PI3K-Akt signaling cascade, owing to its dual role in both survival and mitogenic signaling, is in theory an ideal therapeutic target for this disease, but may also represent its fatal flaw. Thus, largely due to toxicity issues, no PI3K or Akt inhibitors are currently ready for clinical application. In this review, we discuss PI3K-Akt inhibitors as well as inhibitors of pathways and targets both immediately up- and downstream of this cascade, many of which show promise in the clinic.
肾癌，即肾细胞癌，是一种相对罕见的恶性肿瘤，但三分之一的患者在确诊时已发生转移；转移性疾病的预后很差。传统化疗一直效果不佳，因此正在积极评估新型“定制”疗法的靶点。PI3K-Akt信号级联由于其在生存信号和促有丝分裂信号中的双重作用，理论上是这种疾病的理想治疗靶点，但也可能是其致命缺陷。因此，主要由于毒性问题，目前尚无PI3K或Akt抑制剂可用于临床应用。在本综述中，我们讨论了PI3K-Akt抑制剂以及该信号级联上下游的信号通路和靶点的抑制剂，其中许多在临床上显示出前景。
