Tabruyn Sebastien P, Griffioen Arjan W
Angiogenesis Laboratory, Department of Pathology, School for Oncology and Developmental Biology (GROW), University of Maastricht & University Hospital, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
Angiogenesis. 2008;11(1):101-6. doi: 10.1007/s10456-008-9094-4. Epub 2008 Feb 19.
Angiogenesis is considered a promising target in the treatment of cancer. Most of the angiogenesis inhibitors in late-stage clinical testing or approved for the treatment of cancer act indirectly on endothelial cells. They either neutralize angiogenic growth factors from the circulation or block the signaling pathways activated by these growth factors. Another group of angiogenesis inhibitors are the direct angiostatic compounds. These agents have a direct effect on the endothelium, affecting cellular regulatory pathways, independently of the tumor cells. The reason that this category of agents is lagging behind regarding their translation to the clinic may be the lack of sufficient knowledge on the mechanism of action of these compounds. The transcription factor NF-kappaB has been recently connected with multiple aspects of angiogenesis. In addition, several recent studies report that angiogenesis inhibition is associated to NF-kappaB activation. This is of special interest since in tumor cells NF-kappaB activation has been associated to inhibition of apoptosis and currently novel treatment strategies are being developed based on inhibition of NF-kappaB. The paradigm that systemic NF-kappaB inhibition can serve as an anti-cancer strategy, therefore, might need to be re-evaluated. Based on recent data, it might be speculated that NF-kappaB activation, when performed specifically in endothelial cells, could be an efficient strategy for the treatment of cancer.
血管生成被认为是癌症治疗中一个有前景的靶点。大多数处于临床后期试验或已获批用于癌症治疗的血管生成抑制剂间接作用于内皮细胞。它们要么中和循环中的血管生成生长因子，要么阻断这些生长因子激活的信号通路。另一类血管生成抑制剂是直接的血管生成抑制化合物。这些药物对内皮细胞有直接作用，独立于肿瘤细胞影响细胞调节通路。这类药物在向临床转化方面滞后的原因可能是对这些化合物的作用机制缺乏足够的了解。转录因子核因子-κB（NF-κB）最近与血管生成的多个方面相关联。此外，最近的几项研究报告称血管生成抑制与NF-κB激活有关。这一点特别值得关注，因为在肿瘤细胞中NF-κB激活与细胞凋亡抑制相关，目前基于抑制NF-κB正在开发新的治疗策略。因此，全身抑制NF-κB可作为一种抗癌策略的范例可能需要重新评估。基于最近的数据，可以推测，当在内皮细胞中特异性地进行NF-κB激活时，可能是一种有效的癌症治疗策略。
