Division of Endocrinology, Diabetes and Bone Disease, Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L. Levy Place, New York, New York 10029, USA.
Endocrinology. 2011 Jul;152(7):2546-51. doi: 10.1210/en.2011-0231. Epub 2011 May 3.
In recent years, the influence of the IGF system and insulin on cancer growth has been widely studied. Observational human studies have reported increased cancer mortality in those with obesity and type 2 diabetes, which may be attributable to hyperinsulinemia, elevated IGF-I, or potentially both factors. Conversely, those with low insulin, IGF-I and IGF-II levels appear to be relatively protected from cancer development. Initial attention focused on the role of IGF-I in tumor development. The results of these investigations allowed for the development of therapies targeting the IGF-I receptor signaling pathway. However, after in vitro and in vivo studies demonstrating that insulin may also play a significant and independent role in tumorigenesis, insulin is now receiving more attention in this regard. Some studies suggest that targeting insulin receptor signaling may be an important alternative or adjunct to targeting IGF-I receptor signaling. In this minireview, we discuss some of the recent in vitro, animal, and clinical studies that have elaborated our understanding of the influence of IGF and insulin on tumorigenesis. These studies have shed more light on the interaction between insulin and IGF signaling in cancer cells. They have made possible the development of novel targeted therapies and highlighted some of the potential future directions for research and therapeutics.
近年来，IGF 系统和胰岛素对癌症生长的影响受到了广泛研究。观察性人体研究报告称，肥胖和 2 型糖尿病患者的癌症死亡率增加，这可能归因于高胰岛素血症、IGF-I 升高，或者可能是这两个因素共同作用的结果。相反，那些胰岛素、IGF-I 和 IGF-II 水平较低的人似乎相对不易患癌症。最初的研究重点是 IGF-I 在肿瘤发展中的作用。这些研究的结果促成了针对 IGF-I 受体信号通路的治疗方法的发展。然而，在体外和体内研究表明胰岛素也可能在肿瘤发生中发挥重要且独立的作用后，胰岛素在这方面受到了更多的关注。一些研究表明，靶向胰岛素受体信号可能是一种重要的替代或辅助方法，以靶向 IGF-I 受体信号。在这篇简评中，我们讨论了一些最近的体外、动物和临床研究，这些研究阐述了我们对 IGF 和胰岛素对肿瘤发生的影响的理解。这些研究更深入地了解了胰岛素和 IGF 信号在癌细胞中的相互作用。它们为开发新的靶向治疗方法提供了可能，并强调了研究和治疗的一些潜在未来方向。
