Missiaen Rindert, Morales-Rodriguez Francisco, Eelen Guy, Carmeliet Peter
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium.
Vascul Pharmacol. 2017 Mar;90:8-18. doi: 10.1016/j.vph.2017.01.001. Epub 2017 Jan 7.
Current anti-angiogenic therapies in malignant and ocular diseases target growth factor signaling in order to attenuate excessive vascular growth. Although initial responses are promising, overall therapeutic success is limited due to insufficient efficiency, tumor refractoriness and resistance. Emerging evidence suggests that diverse growth factor signaling pathways in endothelial cells (ECs) converge onto cellular metabolism, creating an attractive target for novel alternative anti-angiogenic therapies. Recent studies show that ECs rely on glycolysis for ATP and biomass synthesis, necessary for proliferation and migration, key processes of angiogenesis. In addition, fatty acid β-oxidation (FAO) is essential for de novo nucleotide synthesis during EC proliferation. Initial proof-of-evidence has been given that administration of pharmacological inhibitors of those metabolic pathways can be used to inhibit pathological angiogenesis in vivo. Deciphering the role of other metabolic pathways and exploring the therapeutic potential of blocking these pathways await further investigation.
当前用于恶性疾病和眼部疾病的抗血管生成疗法旨在通过靶向生长因子信号传导来减弱过度的血管生长。尽管初始反应很有前景，但由于效率不足、肿瘤难治性和耐药性，总体治疗成功率有限。新出现的证据表明，内皮细胞（ECs）中多种生长因子信号通路汇聚到细胞代谢上，为新型替代抗血管生成疗法创造了一个有吸引力的靶点。最近的研究表明，内皮细胞依靠糖酵解来合成ATP和生物量，这是增殖和迁移（血管生成的关键过程）所必需的。此外，脂肪酸β氧化（FAO）对于内皮细胞增殖期间的从头核苷酸合成至关重要。已经有初步证据表明，给予这些代谢途径的药理学抑制剂可用于体内抑制病理性血管生成。解读其他代谢途径的作用并探索阻断这些途径的治疗潜力还有待进一步研究。
