Sheba Medical Center, Tel Hashomer, Israel.
Oncology (Williston Park). 2011 May;25(6):518-26, 529.
Insulin-like growth factor 1 (IGF-1)-directed therapy is currently at a crossroads. After decades of research, several agents targeting the IGF pathway are now in clinical trials. One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement. Clinical trials for patients with sarcoma have demonstrated impressive anti-tumor activity in cases where the IGF-1 pathway is activated, such as in Ewing sarcoma; however, acquired resistance has been common. Recently, randomized phase II trials combining IGF-1 R with epidermal grown factor receptor (EGFR) inhibition in colorectal cancer have been completed. Preclinical studies have indicated that several biomarkers may have potential predictive value. Studies of IGF-1R inhibitors in gastrointestinal cancers are currently ongoing in pancreatic, gastroesophageal, hepatocellular, and colorectal cancers. A critical analysis of prior work in this field and a rational strategy for maximizing success on the basis of biomarker use are necessary.
胰岛素样生长因子 1（IGF-1）靶向治疗正处于十字路口。经过几十年的研究，目前已有几种针对 IGF 途径的药物进入临床试验。最近，一项 IGF-1R 抑制剂 figitumumab 治疗非小细胞肺癌的 III 期临床试验在中期分析显示无生存改善后停止。针对肉瘤患者的临床试验表明，在 IGF-1 途径激活的情况下，如尤文肉瘤，该药物具有显著的抗肿瘤活性；然而，获得性耐药很常见。最近，针对结直肠癌的 IGF-1R 与表皮生长因子受体（EGFR）抑制联合的随机 II 期临床试验已经完成。临床前研究表明，几种生物标志物可能具有潜在的预测价值。目前正在进行 IGF-1R 抑制剂在胰腺癌、胃食管、肝细胞和结直肠癌中的研究。对该领域先前工作的批判性分析以及基于生物标志物使用最大化成功的合理策略是必要的。
