Targeting HIF-1 for cancer therapy

被引:5430
作者
Semenza, GL [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA
关键词
D O I
10.1038/nrc1187
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.
引用
收藏
页码:721 / 732
页数:12
相关论文
共 109 条
  • [61] 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF
    Mabjeesh, NJ
    Escuin, D
    LaVallee, TM
    Pribluda, VS
    Swartz, GM
    Johnson, MS
    Willard, MT
    Zhong, H
    Simons, JW
    Giannakakou, P
    [J]. CANCER CELL, 2003, 3 (04) : 363 - 375
  • [62] Mabjeesh NJ, 2002, CANCER RES, V62, P2478
  • [63] Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth
    Mack, FA
    Rathmell, WK
    Arsham, AM
    Gnarra, J
    Keith, B
    Simon, MC
    [J]. CANCER CELL, 2003, 3 (01) : 75 - 88
  • [64] FIH-1:: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity
    Mahon, PC
    Hirota, K
    Semenza, GL
    [J]. GENES & DEVELOPMENT, 2001, 15 (20) : 2675 - 2686
  • [65] Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3α locus
    Makino, Y
    Kanopka, A
    Wilson, WJ
    Tanaka, H
    Poellinger, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (36) : 32405 - 32408
  • [66] HIF activation identifies early lesions in VHL kidneys: Evidence for site-specific tumor suppressor function in the nephron
    Mandriota, SJ
    Turner, KJ
    Davies, DR
    Murray, PG
    Morgan, NV
    Sowter, HM
    Wykoff, CC
    Maher, ER
    Harris, AL
    Ratcliffe, PJ
    Maxwell, PH
    [J]. CANCER CELL, 2002, 1 (05) : 459 - 468
  • [67] Mankoff DA, 2002, J NUCL MED, V43, P500
  • [68] The contribution of VHL substrate binding and HIF1-α to the phenotype of VHL loss in renal cell carcinoma
    Maranchie, JK
    Vasselli, JR
    Riss, J
    Bonifacino, JS
    Linehan, WM
    Klausner, RD
    [J]. CANCER CELL, 2002, 1 (03) : 247 - 255
  • [69] Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation
    Masson, N
    Willam, C
    Maxwell, PH
    Pugh, CW
    Ratcliffe, PJ
    [J]. EMBO JOURNAL, 2001, 20 (18) : 5197 - 5206
  • [70] The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    Maxwell, PH
    Wiesener, MS
    Chang, GW
    Clifford, SC
    Vaux, EC
    Cockman, ME
    Wykoff, CC
    Pugh, CW
    Maher, ER
    Ratcliffe, PJ
    [J]. NATURE, 1999, 399 (6733) : 271 - 275