Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy.
Curr Top Med Chem. 2021;21(1):73-86. doi: 10.2174/1568026620666201126163436.
Angiogenesis is a key process allowing the formation of blood vessels. It is crucial for all the tissues and organs, ensuring their function and growth. Angiogenesis is finely controlled by several mechanisms involving complex interactions between pro- or antiangiogenic factors, and an imbalance in this control chain may result in pathological conditions. Metals as copper, zinc and iron cover an essential role in regulating angiogenesis, thus therapies having physiological metals as target have been proposed. In addition, some complexes of heavier metal ions (e.g., Pt, Au, Ru) are currently used as established or experimental anticancer agents targeting genomic or non-genomic targets. These molecules may affect the angiogenic mechanisms determining different effects that have been only poorly and non-systematically investigated so far. Accordingly, in this review article, we aim to recapitulate the impact on the angiogenic process of some reference anticancer drugs, and how it is connected to the overall pharmacological effects. In addition, we highlight how the activity of these drugs can be related to the role of biological essential metal ions. Overall, this may allow a deeper description and understanding of the antineoplastic activity of both approved or experimental metal complexes, providing important insights for the synthesis of new inorganic drugs able to overcome resistance and recurrence phenomena.
血管生成是允许血管形成的关键过程。它对于所有的组织和器官都是至关重要的，确保它们的功能和生长。血管生成受到几种机制的精细控制，这些机制涉及促血管生成或抗血管生成因子之间的复杂相互作用，而这种控制链的失衡可能导致病理状况。铜、锌和铁等金属在调节血管生成方面起着重要作用，因此已经提出了以生理金属为靶点的治疗方法。此外，一些较重的金属离子（如铂、金、钌）的配合物目前被用作针对基因组或非基因组靶点的既定或实验性抗癌药物。这些分子可能会影响决定不同效果的血管生成机制，而迄今为止，这些效果仅得到了很少且非系统的研究。因此，在这篇综述文章中，我们旨在总结一些参考抗癌药物对血管生成过程的影响，以及它与整体药理作用的关系。此外，我们还强调了这些药物的活性如何与生物必需金属离子的作用相关。总的来说，这可能允许对已批准或实验性金属配合物的抗肿瘤活性进行更深入的描述和理解，为合成能够克服耐药性和复发现象的新型无机药物提供重要的见解。
