Department of Neurosurgery, Diller Cancer Research Building, University of California at San Francisco (UCSF), San Francisco, CA, USA.
Autophagy. 2012 Jun;8(6):979-81. doi: 10.4161/auto.20232. Epub 2012 Jun 1.
While anti-angiogenic therapy was initially greeted enthusiastically by the cancer community, initial successes with this therapeutic modality were tempered by the failure of angiogenesis inhibitors to produce sustained clinical responses in most patients, with resistance to the inhibitors frequently developing. We recently reported that hypoxia increases after the devascularization caused by anti-angiogenic therapy, consistent with the goals of these therapies, but that some tumor cells become resistant and survive the hypoxic insult elicited by anti-angiogenic therapy through autophagy by activating both AMPK and HIF1A pathways. These findings suggest that modulating the autophagy pathway may someday allow anti-angiogenic therapy to fulfill its therapeutic potential. However, further work will clearly be needed to develop more potent and specific autophagy inhibitors and to better understand the regulators of autophagy in malignant cells.
虽然抗血管生成治疗最初受到癌症学界的热烈欢迎，但这种治疗方式的初步成功因血管抑制剂在大多数患者中未能产生持续的临床反应而受到影响，而抑制剂的耐药性经常出现。我们最近报道称，抗血管生成治疗引起的血管缺血后，肿瘤组织中的缺氧增加，这与这些治疗方法的目标一致，但一些肿瘤细胞通过自噬对缺氧损伤产生抵抗并存活下来，自噬通过激活 AMPK 和 HIF1A 通路。这些发现表明，调节自噬途径可能有一天使抗血管生成治疗能够发挥其治疗潜力。然而，显然需要进一步的工作来开发更有效和更特异的自噬抑制剂，并更好地理解恶性细胞中自噬的调节因子。
