CEDOC, Chronic Diseases Research Centre, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Lisbon, Portugal.
Adv Exp Med Biol. 2020;1219:143-159. doi: 10.1007/978-3-030-34025-4_8.
Effective therapies to fight cancer should not be focused specifically on cancer cells, but it should consider the various components of the TME. Non-cancerous cells cooperate with cancer cells by sharing signaling and organic molecules, accounting for cancer progression. Most of the anti-angiogenic therapy clinically approved for the treatment of human diseases relies on targeting vascular endothelial growth factor (VEGF) signaling pathway. Unexpectedly and unfortunately, the results of anti-angiogenic therapies in the treatment of human diseases are not so effective, showing an insufficient efficacy and resistance.This chapter will give some insights on showing that targeting endothelial cell metabolism is a missing piece to revolutionize cancer therapy. Only recently endothelial cell (EC) metabolism has been granted as an important inducer of angiogenesis. Metabolic studies in EC demonstrated that targeting EC metabolism can be an alternative to overcome the failure of anti-angiogenic therapies. Hence, it is urgent to increase the knowledge on how ECs alter their metabolism during human diseases, in order to open new therapeutic perspectives in the treatment of pathophysiological angiogenesis, as in cancer.
有效的癌症治疗方法不应仅针对癌细胞，而应考虑 TME 的各个组成部分。非癌细胞通过共享信号和有机分子与癌细胞合作，导致癌症进展。大多数临床上批准用于治疗人类疾病的抗血管生成疗法依赖于靶向血管内皮生长因子 (VEGF) 信号通路。出乎意料的是，抗血管生成疗法在治疗人类疾病中的效果并不理想，显示出疗效不足和耐药性。本章将提供一些见解，表明靶向内皮细胞代谢是彻底改变癌症治疗的缺失环节。直到最近，内皮细胞 (EC) 代谢才被认为是促进血管生成的重要诱导因素。在 EC 中的代谢研究表明，靶向 EC 代谢可以作为克服抗血管生成疗法失败的一种替代方法。因此，迫切需要增加关于 EC 在人类疾病期间如何改变其代谢的知识，以便为治疗生理病理性血管生成（如癌症）开辟新的治疗前景。
