Rapisarda Annamaria, Shoemaker Robert H, Melillo Giovanni
Developmental Therapeutics Program, Science Applications International Corporation, Frederick, Inc; National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Cell Cycle. 2004 Feb;3(2):172-5.
HIF-1 is a key factor in cancer progression. Efforts are underway to identify and develop small molecules that inhibit HIF-1 transcriptional activity. What are the best targets and the best ways to develop HIF-1 inhibitors are open questions. However, several "nonselective" HIF-1 inhibitors have been identified, which are either in the clinic or under development. In this article, we discuss how topoisomerase I poisons, which inhibit HIF-1a protein accumulation and transcriptional activity, can be "rationally" used to target HIF-1 for cancer therapy.
缺氧诱导因子-1（HIF-1）是癌症进展中的关键因素。目前正在努力识别和开发抑制HIF-1转录活性的小分子。开发HIF-1抑制剂的最佳靶点和最佳方法仍是悬而未决的问题。然而，已经鉴定出几种“非选择性”HIF-1抑制剂，它们要么正在临床试验中，要么正在研发中。在本文中，我们讨论了拓扑异构酶I抑制剂如何“合理地”用于靶向HIF-1进行癌症治疗，这类抑制剂可抑制HIF-1α蛋白积累和转录活性。
