The Type 1 Insulin-Like Growth Factor Receptor Pathway
The Type 1 Insulin-Like Growth Factor Receptor Pathway
复制标题
DOI：
10.1158/1078-0432.ccr-07-4879
复制
发表时间：
2008-10-15
影响因子：
11.5
通讯作者：
Macaulay, Valentine M.
中科院分区：
文献类型：
--
作者：
Chitnis, Meenali M.;Yuen, John S. P.;Macaulay, Valentine M.
过去二十年进行的研究表明，1型胰岛素样生长因子受体（IGF1R）在肿瘤发生、转移和对现有癌症治疗形式的耐药性中的重要性。然而，IGF1R本身最近才被接受为可信的治疗靶点，这可能反映了正常组织IGF1R表达以及与胰岛素受体的密切同源性对药物设计造成的潜在问题。目前类似的12种抗IGF1R疗法正在进行临床评估，包括阻断抗体和酪氨酸激酶抑制剂。本综述将总结IGF1R激活的主要信号通路和临床前数据，验证这种受体作为治疗靶点，我们将审查在测试IGF1R抑制药物候选人的临床进展，相对的好处和潜在的毒性的胰岛素受体的共抑制，并结合IGF1R阻断与其他癌症治疗的理由。IGF1R信号的理解是重要的，因为它将指导适当的分子标记物纳入临床试验设计。这将是识别最有可能受益的患者的关键，因此将影响IGF1 R抑制从实验干预过渡到临床治疗的能力。
Research conducted over the past two decades has shown the importance of the type 1 insulin-like growth factor receptor (IGF1R) in tumorigenesis, metastasis, and resistance to existing forms of cancer therapy. The IGF1R itself has only recently been accepted as a credible treatment target, however, perhaps reflecting the potential problems for drug design posed by normal tissue IGF1R expression, and close homology with the insulin receptor. Currently similar to 12 anti-IGF1R therapeutics are undergoing clinical evaluation, including blocking antibodies and tyrosine kinase inhibitors. This review will summarize the principal signaling pathways activated by IGF1R and the preclinical data that validated this receptor as a treatment target.We will review clinical progress in the testing of IGF1R inhibitory drug candidates, the relative benefits and potential toxicities of coinhibition of the insulin receptor, and the rationale for combining IGF1R blockade with other cancer treatments. An understanding of IGF1R signaling is important because it will guide the incorporation of appropriate molecular markers into clinical trial design. This will be key to the identification of patients most likely to benefit, and so will influence the ability of IGF1R inhibition to make the transition from experimental intervention to clinical therapy.