Department of Medical Oncology, Santa Maria della Misericordia Hospital, Piazzale L. Severi n. 1, 06132, Perugia, Italy.
Department of Medicine, University of Perugia, Piazzale L. Severi n. 1, 06132, Perugia, Italy.
Semin Cancer Biol. 2019 Jun;56:87-99. doi: 10.1016/j.semcancer.2017.11.005. Epub 2017 Nov 8.
Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, anti-vascular endothelial growth factor monoclonal antibodies, such as bevacizumab and ramucirumab, and receptor tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, regorafenib and axitinib) have had a profound impact on the way we treat patients with advanced cancer, providing in some cases unprecedented clinical benefit. The molecular mechanisms underlying tumor-driven angiogenesis have been explored extensively and have unveiled a number of potential clinically relevant targets, including several novel enzymes. In this review, we summarized the current strategies to target tumor-driven angiogenesis through the inhibition of relevant and selected classes of enzymes involved in this process.
血管生成在癌症进展中起着关键作用，是组织侵袭和转移所必需的。从 1971 年福克曼的初步观察开始，基础研究继续为这个多方面的过程提供新的分子见解，导致了几种抗血管生成药物的发展。迄今为止，抗血管内皮生长因子单克隆抗体，如贝伐珠单抗和雷莫芦单抗，以及受体酪氨酸激酶抑制剂（如索拉非尼、舒尼替尼、瑞戈非尼和阿昔替尼）对我们治疗晚期癌症的方式产生了深远的影响，在某些情况下提供了前所未有的临床获益。肿瘤驱动的血管生成的分子机制已经被广泛探索，并揭示了一些潜在的具有临床相关性的靶点，包括一些新的酶。在这篇综述中，我们总结了通过抑制参与这一过程的相关和选定类别的酶来靶向肿瘤驱动的血管生成的当前策略。
