Kizaka-Kondoh Shinae, Tanaka Shotaro, Harada Hiroshi, Hiraoka Masahiro
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Adv Drug Deliv Rev. 2009 Jul 2;61(7-8):623-32. doi: 10.1016/j.addr.2009.01.006. Epub 2009 May 3.
Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions, so-called tumor hypoxia. Although more than half a century has passed since it was suggested that tumor hypoxia correlated with bad treatment outcomes and contributed to the recurrence of cancer, no fundamental solution to this problem has yet been found. Hypoxia-inducible factor HIF-1 is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes, whose function is strongly associated with the malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important therapeutic targets of cancer therapy, particularly in the therapy against refractory cancers. Therefore targeting strategies to overcome the HIF-1-active microenvironment are important for cancer therapy.
实体瘤具有独特的微环境,会经历慢性缺氧状态,即所谓的肿瘤缺氧。尽管自提出肿瘤缺氧与不良治疗结果相关并导致癌症复发以来已过去半个多世纪,但尚未找到解决这一问题的根本办法。缺氧诱导因子HIF-1是调节细胞对缺氧反应的主要转录因子。它诱导多种基因,这些基因的功能与整个肿瘤的恶性改变密切相关。HIF-1诱导的细胞变化是癌症治疗的极其重要的治疗靶点,尤其是在难治性癌症的治疗中。因此,克服HIF-1活性微环境的靶向策略对癌症治疗很重要。