Lady Davis Research Institute and McGill University, Montreal, Quebec H3T1E2, Canada.
Nat Rev Cancer. 2012 Feb 16;12(3):159-69. doi: 10.1038/nrc3215.
Although several early phase clinical trials raised enthusiasm for the use of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, initial Phase III results in unselected patients have been disappointing. Further clinical studies may benefit from the use of predictive biomarkers to identify probable responders, the use of rational combination therapies and the consideration of alternative targeting strategies, such as ligand-specific antibodies and receptor-specific tyrosine kinase inhibitors. Targeting insulin and IGF signalling also needs to be considered in the broader context of the pathophysiology that relates obesity and diabetes to neoplasia, and the effects of anti-diabetic drugs, including metformin, on cancer risk and prognosis. The insulin and IGFI receptor family is also relevant to the development of PI3K-AKT pathway inhibitors.
尽管几项早期临床试验对使用胰岛素样生长因子 I 受体 (IGF1R)-特异性抗体治疗癌症产生了热情，但最初在未选择患者中的 III 期结果令人失望。进一步的临床研究可能受益于使用预测性生物标志物来识别可能的应答者，使用合理的联合治疗以及考虑替代靶向策略，如配体特异性抗体和受体特异性酪氨酸激酶抑制剂。在与肥胖和糖尿病与肿瘤发生相关的病理生理学的更广泛背景下，以及包括二甲双胍在内的抗糖尿病药物对癌症风险和预后的影响下，靶向胰岛素和 IGF 信号也需要被考虑。胰岛素和 IGFI 受体家族也与 PI3K-AKT 通路抑制剂的发展相关。
