Larsson O, Girnita A, Girnita L
Department of Oncology and Pathology, CCK R8:04, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Br J Cancer. 2005 Jun 20;92(12):2097-101. doi: 10.1038/sj.bjc.6602627.
The insulin-like growth factor (IGF-1) signalling is highly implicated in cancer. In this signalling the IGF-1 receptor (IGF-1R) is unquestionable, the predominating single factor. IGF-1R is crucial for tumour transformation and survival of malignant cell, but is only partially involved in normal cell growth. This is in part due to the interactions with oncogenes. Recent findings suggest a close interplay with the p53/MDM2 pathway. Disturbances in components in the p53/MDM2/IGF-1R network may cause IGF-1R upregulation and growth advantage for the cancer cell. Targeting of IGF-1R is more and more seen as a promising option for future cancer therapy. Single chain antibodies and small molecules with selective effects on IGF-1R dependent malignant growth are of particular interest. Forthcoming clinical trials are welcome and will indeed be the only way to evaluate the impact of IGF-1R targeting in human cancer.
胰岛素样生长因子(IGF-1)信号传导与癌症密切相关。在该信号传导中,胰岛素样生长因子-1受体(IGF-1R)无疑是主要的单一因子。IGF-1R对肿瘤转化和恶性细胞存活至关重要,但仅部分参与正常细胞生长。这部分是由于与癌基因的相互作用。最近的研究结果表明,它与p53/MDM2通路存在密切相互作用。p53/MDM2/IGF-1R网络中各成分的紊乱可能导致IGF-1R上调,并赋予癌细胞生长优势。靶向IGF-1R越来越被视为未来癌症治疗的一个有前景的选择。对依赖IGF-1R的恶性生长具有选择性作用的单链抗体和小分子尤其令人关注。即将开展的临床试验是值得欢迎的,而且确实将是评估靶向IGF-1R对人类癌症影响的唯一途径。