Boone David N, Lee Adrian V
Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Crit Rev Oncog. 2012;17(2):161-73. doi: 10.1615/critrevoncog.v17.i2.30.
Overwhelming evidence implicates insulin-like growth factor (IGF) signaling in the growth and survival of many types of human cancer cells. Numerous inhibitors of the IGF1 receptor (IGF1R) have been developed, and they displayed remarkable antineoplastic activity in preclinical models and promising success in early phase clinical trials. However, while responses have been observed in numerous cancer types, they have occurred in a minority of patients, and serious toxicities have been observed. Identifying patients likely to benefit from anti-IGF1R therapy requires further characterizing the role of IGF1 signaling in various stages of tumorigenesis in order to identify critical downstream factors that may be used as predictors of response, or to serve as novel therapeutic targets. Recent microarray analyses have begun to unravel expression "signatures" specific for IGF1 that correlate with poor breast cancer prognosis and with response to anti-IGFIR inhibitors. In this review we briefly discuss the history of the IGF1 family in neoplasia, how it is targeted, results from clinical trials, and the quest for biomarkers that will predict response to IGF1R-targeted therapy.
大量证据表明，胰岛素样生长因子（IGF）信号传导与多种人类癌细胞的生长和存活有关。已经开发出许多胰岛素样生长因子1受体（IGF1R）抑制剂，它们在临床前模型中显示出显著的抗肿瘤活性，并在早期临床试验中取得了令人鼓舞的成功。然而，虽然在多种癌症类型中都观察到了反应，但只有少数患者出现了这种情况，并且还观察到了严重的毒性。确定可能从抗IGF1R治疗中受益的患者需要进一步阐明IGF1信号传导在肿瘤发生各个阶段的作用，以便确定可能用作反应预测指标或作为新治疗靶点的关键下游因子。最近的微阵列分析已开始揭示与乳腺癌预后不良以及对抗IGFIR抑制剂的反应相关的、特定于IGF1的表达“特征”。在本综述中，我们简要讨论了IGF1家族在肿瘤形成中的历史、其靶向方式、临床试验结果以及寻找可预测对IGF1R靶向治疗反应的生物标志物的情况。
