Morgensztern Daniel, McLeod Howard L
Washington University School of Medicine, Department of Medicine, St Louis Veteran's Administration Medical Center, St Louis, Missouri 63110, USA.
Anticancer Drugs. 2005 Sep;16(8):797-803. doi: 10.1097/01.cad.0000173476.67239.3b.
The PI3K/Akt/mTOR pathway regulates several normal cellular functions that are also critical for tumorigenesis, including cellular proliferation, growth, survival and mobility. Components of this pathway are frequently abnormal in a variety of tumors, making them an attractive target for anti-cancer therapy. Inhibition of mTOR in patients with cancer became more feasible after the development of rapamycin analogs with improved pharmacologic properties. The promising activity of these agents in early clinical trials has led to the development of ongoing phase III trials in renal cell carcinoma and breast cancer. Future studies are needed to identify the patients most likely to benefit from this form of therapy, and to define its role in combination with chemotherapy, hormones and growth factor inhibitors.
PI3K/Akt/mTOR信号通路调节多种对肿瘤发生至关重要的正常细胞功能,包括细胞增殖、生长、存活和迁移。该信号通路的组成部分在多种肿瘤中常常出现异常,使其成为抗癌治疗的一个有吸引力的靶点。随着具有改善药理特性的雷帕霉素类似物的开发,在癌症患者中抑制mTOR变得更加可行。这些药物在早期临床试验中的良好活性已促使针对肾细胞癌和乳腺癌的III期临床试验正在开展。需要进一步的研究来确定最有可能从这种治疗形式中获益的患者,并明确其与化疗、激素和生长因子抑制剂联合使用时的作用。