Role of hypoxia-inducible factor-1α as a cancer therapy target
Role of hypoxia-inducible factor-1α as a cancer therapy target
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DOI：
10.1677/erc.1.01290
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发表时间：
2006-12-01
影响因子：
3.9
通讯作者：
Harris, Adrian L.
中科院分区：
文献类型：
--
作者：
Patiar, Shalini;Harris, Adrian L.
由于肿瘤生长和血管生成之间的不匹配，实体瘤中发生缺氧。实体瘤中的缺氧与侵袭性表型以及对放疗和化疗的抵抗相关，导致患者预后不良。缺氧诱导因子-1 (HIF-1) 是一种转录因子，它会因肿瘤内缺氧而被激活，并且是基因改变的结果，激活癌基因并使抑癌基因失活。它通过激活基因转录，在肿瘤细胞适应缺氧过程中发挥关键作用，从而调节多种生物过程，包括血管生成、细胞增殖和存活、葡萄糖代谢、pH调节和迁移。这使得 HIF-1 成为抗癌药物开发的一个有吸引力的靶点。这些药物的成功取决于可靠的方法来识别最有可能从 HIF-1 靶向治疗中受益的患者。几种新型 HIF-1 小分子抑制剂已被鉴定并正在进行临床试验，但这些抑制剂都不是针对 HIF-1 的。进一步的工作正在进行中，以确定更具选择性的 HIF-1 抑制剂。
Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is activated in response to intratumoural hypoxia and as a result of genetic alterations that activate oncogenes and inactivate tumour suppressor genes. It plays a key role in the adaptation of tumour cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation and survival, glucose metabolism, pH regulation and migration. This makes HIF-1 an attractive target for the development of anticancer agents. The success of these agents depends on reliable methods to identify those patients most likely to benefit from HIF-1-targeted therapy. Several novel small molecule inhibitors of HIF-1 have been identified and are moving towards clinical trials, but none of these are specific for HIF-1. Further work is ongoing to identify more selective HIF-1 inhibitors.