Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance.
Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance.
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DOI：
10.1016/j.gendis.2014.10.004
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发表时间：
2015-03-01
期刊：
影响因子：
6.8
通讯作者：
Luu, Hue H
中科院分区：
文献类型：
--
作者：
Denduluri, Sahitya K;Idowu, Olumuyiwa;Wang, Zhongliang;Liao, Zhan;Yan, Zhengjian;Mohammed, Maryam K;Ye, Jixing;Wei, Qiang;Wang, Jing;Zhao, Lianggong;Luu, Hue H
目前癌症治疗的最大障碍之一是肿瘤的耐药性。尽管最近在诊断实践和手术干预方面取得了进展，但许多肿瘤对辅助或新辅助放疗和化疗的反应较差。因此，许多患有这些侵袭性癌症的患者的预后仍然黯淡。胰岛素样生长因子（IGF）信号轴已被证明在各种肿瘤的发生和发展中发挥关键作用。许多基础科学和转化研究表明，IGF通路调节剂在治疗各种恶性肿瘤时具有良好的效果。最近也有大量证据表明，IGF信号失调与肿瘤对当前标准治疗的反应减弱有关。通过更好地了解IGF依赖性和非依赖性通路成员影响药物敏感性的机制，我们最终可以利用IGF信号的调节剂来增强当前治疗的效果。这篇综述总结和综合了最近关于IGF通路在耐药性中的作用的许多研究。我们简要概述了IGF信号及其在肿瘤中的一般作用，然后深入研究了许多类型的人类癌症，这些癌症已被证明具有IGF通路参与对治疗的抵抗和/或致敏。最终，我们的希望是，这样的证据汇编将迫使研究人员开展迫切需要的研究，寻找与IGF信号调节剂联合治疗的方法，以克服目前的治疗耐药性。
One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies. There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy. By better understanding both the IGF-dependent and -independent mechanisms by which pathway members can influence drug sensitivity, we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy. This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance. We offer a brief overview of IGF signaling and its general role in neoplasia, and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy. Ultimately, our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.