Zeng Xianke, Yee Douglas
Department of Pharmacology, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
Adv Exp Med Biol. 2007;608:101-12. doi: 10.1007/978-0-387-74039-3_7.
Despite improvements in breast cancer therapy in recent years, additional therapies need to be developed. New therapies may have activity by themselves or may have utility in combination with other agents. Population, preclinical, and basic data suggest the insulin-like growth factor (IGF) system functions to maintain the malignant phenotype in breast cancer. Since the IGFs act via transmembrane tyrosine kinase receptors, targeting of the key receptors could provide a new pathway in breast cancer. In addition, IGF action enhances cell survival, so combination of anti-IGF therapy with conventional cytotoxic drugs could lead to synergistic effects. In this review, we will discuss the rationale for targeting the IGF system, potential methods to disrupt IGF signaling, and identify potential interactions between IGF inhibitors and other anti-tumor strategies. We will also identify important issues to consider when designing clinical trials.
尽管近年来乳腺癌治疗有所改善，但仍需要开发更多疗法。新疗法可能自身就具有活性，或者与其他药物联合使用时可能具有效用。群体、临床前和基础数据表明，胰岛素样生长因子（IGF）系统在维持乳腺癌的恶性表型方面发挥作用。由于IGF通过跨膜酪氨酸激酶受体发挥作用，靶向关键受体可能为乳腺癌提供一条新途径。此外，IGF作用可增强细胞存活，因此抗IGF疗法与传统细胞毒性药物联合使用可能产生协同效应。在本综述中，我们将讨论靶向IGF系统的基本原理、破坏IGF信号传导的潜在方法，并确定IGF抑制剂与其他抗肿瘤策略之间的潜在相互作用。我们还将确定设计临床试验时需要考虑的重要问题。
