Am J Transl Res. 2009 Jan 30;1(2):101-14.
Lung cancer leads all other cancers in both incidence and mortality. Recent advances in underlying molecular pathogenesis have validated a panel of protein tyrosine kinases as new targets in lung cancer treatment. Insulin-like growth factor-1 receptor (IGF-1R) is an important tyrosine kinase receptor involved in cell proliferation, differentiation, metabolism, apoptosis, and angiogenesis. Aberrant activation of IGF-1R is frequently found in patients with lung cancer and contributes to malignant transformation and poor prognosis for patients with lung cancer. In this review, we focused on recent progress in the research of IGF-1R's role in lung cancer development and progression, including its structure and biological function, potential mechanisms of aberrant activation, and related oncogenic effects. We also discussed effective IGF-1R antagonists that are currently registered for clinic trials or are undergoing preclinical study with special emphasis on their antibodies and small molecule tyrosine kinase inhibitors.
肺癌在发病率和死亡率方面均位居所有癌症之首。近年来,有关其潜在分子发病机制的研究取得了进展,一系列蛋白酪氨酸激酶已被证实为肺癌治疗的新靶点。胰岛素样生长因子-1 受体(IGF-1R)是一种重要的酪氨酸激酶受体,参与细胞增殖、分化、代谢、凋亡和血管生成。在肺癌患者中常发现 IGF-1R 的异常激活,这有助于肺癌的恶性转化和患者预后不良。在这篇综述中,我们重点关注 IGF-1R 在肺癌发生和发展中的作用的最新研究进展,包括其结构和生物学功能、异常激活的潜在机制以及相关致癌效应。我们还讨论了目前正在临床试验注册或正在进行临床前研究的有效 IGF-1R 拮抗剂,特别强调了它们的抗体和小分子酪氨酸激酶抑制剂。