Deciphering the role of insulin-like growth factor-I receptor in trastuzumab resistance.
Deciphering the role of insulin-like growth factor-I receptor in trastuzumab resistance.
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DOI：
10.1155/2012/648965
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Nahta R
中科院分区：
文献类型：
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作者：
Nahta R
对 HER2 靶向抗体曲妥珠单抗的耐药性是治疗 HER2 过表达的转移性乳腺癌的一个主要临床问题。据报道，在源自曲妥珠单抗耐药性乳腺癌的细胞系和临床样本中，胰岛素样生长因子-I 受体 (IGF-IR) 的表达或信号传导增加。 IGF-IR 信号传导的遗传和药理学抑制已被证明可以改善曲妥珠单抗初治模型和曲妥珠单抗耐药模型中对曲妥珠单抗的反应。在本文中，我们将讨论 IGF-IR 信号在曲妥珠单抗耐药中的作用。此外，我们将讨论联合靶向 IGF-IR 和 HER2 作为治疗因曲妥珠单抗治疗而进展的 HER2 过度表达乳腺癌的潜在治疗策略。
Resistance to the HER2-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-overexpressing metastatic breast cancer. Increased expression or signaling of the insulin-like growth factor-I receptor (IGF-IR) has been reported in a subset of cell lines and clinical samples derived from trastuzumab-resistant breast cancers. Genetic and pharmacologic inhibition of IGF-IR signaling has been shown to improve response to trastuzumab in trastuzumab-naïve and trastuzumab-resistant models. In this paper, we will discuss the role of IGF-IR signaling in trastuzumab resistance. Further, we will discuss cotargeting IGF-IR and HER2 as a potential therapeutic strategy for HER2-over-expressing breast cancers that have progressed on trastuzumab treatment.