The Effects on Angiogenesis of Relevant Inorganic Chemotherapeutics

Curr Top Med Chem. 2021;21(1):73-86. doi: 10.2174/1568026620666201126163436.

Abstract

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.

Keywords: Angiogenesis; Anticancer metallodrugs; Antimicrobial matallodrugs; Arsenic; Gold; Inorganic drugs; Platinum; Ruthenium.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Humans
  • Metals, Heavy / chemistry
  • Metals, Heavy / pharmacology*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Coordination Complexes
  • Metals, Heavy