Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies

被引:310
作者
Brown, JM [1 ]
机构
[1] Stanford Univ, Sch Med, Canc Biol Res Lab, Stanford, CA 94305 USA
来源
MOLECULAR MEDICINE TODAY | 2000年 / 6卷 / 04期
关键词
D O I
10.1016/S1357-4310(00)01677-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human solid tumours are considerably less well oxygenated than normal tissues, This leads to resistance to radiotherapy and anticancer chemotherapy, as well as predisposing to increased tumour metastases, However, tumour hypoxia can be exploited in cancer treatment. One such strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise, The second way to exploit hypoxia is to take advantage of the selective induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) under hypoxic conditions; gene therapy strategies based on this are in development.
引用
收藏
页码:157 / 162
页数:6
相关论文
共 32 条
  • [1] [Anonymous], 1995, TUMOR OXYGENATION
  • [2] The molecular basis of the hypoxia response pathway: Tumour hypoxia as a therapy target
    Blancher, C
    Harris, AL
    [J]. CANCER AND METASTASIS REVIEWS, 1998, 17 (02) : 187 - 194
  • [3] Brizel DM, 1996, CANCER RES, V56, P941
  • [4] Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck
    Brizel, DM
    Sibley, GS
    Prosnitz, LR
    Scher, RL
    Dewhirst, MW
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1997, 38 (02): : 285 - 289
  • [5] Brown JM, 1999, CANCER RES, V59, P5863
  • [6] SR-4233 (TIRAPAZAMINE) - A NEW ANTICANCER DRUG EXPLOITING HYPOXIA IN SOLID TUMORS
    BROWN, JM
    [J]. BRITISH JOURNAL OF CANCER, 1993, 67 (06) : 1163 - 1170
  • [7] BROWN JM, 1990, CANCER RES, V50, P7745
  • [8] Hypoxia-specific cytotoxins in cancer therapy
    Brown, JM
    Sum, BG
    [J]. SEMINARS IN RADIATION ONCOLOGY, 1996, 6 (01) : 22 - 36
  • [9] Brown JM, 1998, CANCER RES, V58, P1408
  • [10] Delahoussaye Y. M., 1997, Proceedings of the American Association for Cancer Research Annual Meeting, V38, P163