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Beyond DNA as Target for Metal-Based Anticancer Drugs: The Roles of Protein Metalation

Call for Papers

Nowadays, metal complexes represent an essential arsenal in the fight against cancer, with about half of all patients subjected to anticancer chemotherapy being treated with platinum-based drugs. It is nowadays ascertained that despite nuclear DNA is commonly known to be the main target for clinically established Pt drugs, interaction of platinum-based (as well as non-Pt-based) drugs with cellular proteins represents a very important aspect for their pharmacokinetic, bioavailability, and pharmacological effects. Also, there is today increasing awareness that proteins are preferential “binding partners” for several metal-based drugs, according to the so-called “protein metalation process.” Protein metalation may be relevant to accounting for the toxic effects of anticancer metallodrugs (e.g., cisplatin) but also for determining some aspects of their mode of action, using model protein target to compare the reactivity of different complexes with the aim to formulate mechanistic hypothesis. On the other hand, metal-protein interactions may be exploited for downregulation or inhibition of enzymes, with this effect being reachable in different manners, depending on the mode of action and characteristics of the compound and its target. Taking advantage of these aspects, it is possible to exploit metal complexes capable of binding specific amino acids or particular protein’s sites and binding pockets for the inhibition of selected proteins playing key roles in preserving the cellular metabolic as well as redox functions of cancer cells. Indeed, in recent years, selected gold (III) and gold (I) compounds had been reported as promising anticancer agents, characterized by their ability to target the thioredoxin reductase. Remarkably, because of binding and protein’s activity inhibition, a series of perturbations involving redox homeostasis loss leads to the activation of the apoptotic process. Beyond thioredoxin reductase, other proteins may be targeted for therapeutic purposes. This is the case of those involved in protein homeostasis that, in turn, represents a crucial aspect for cancer cells proliferation and survival. In this view, proteasome is today recognized as an important target for innovative gold, zinc, nickel, and copper-based anticancer drugs. With these ideas in mind, it clearly appears how it is possible to exploit the extreme versatility and diversity of transition metals and to design innovative metal-based compounds able to target and impair the activity of specific enzymes (or, more in general, proteins), relevant to cancer growth and proliferation. Targeting proteins with a crucial role in the control of cell growth, as well as survival and malignancy with metal-based drugs, is of paramount importance in controlling and fighting the tumor itself.

This special issue aims to collect original contributions describing and reporting recent advances and developments in the field of metal-based antineoplastic agents that bind to proteins. In particular, the manuscripts focused on the following topics are welcome.

Potential topics include but are not limited to the following:

  • Design and synthesis of novel metal-based anticancer drugs that bind to protein targets
  • Study of mechanistic aspects involved in protein metalation
  • New protein targets for metal-based anticancer drugs
  • Metal-based drugs and anticancer properties in human tumor cell lines
  • Metal-based drugs and protein targets in cancer therapy: mechanistic and clinical studies
  • Identification of drug metalation targets on cancer proteome using high-throughput technologies

Authors can submit their manuscripts through the Manuscript Tracking System at

Submission DeadlineFriday, 29 June 2018
Publication DateNovember 2018

Papers are published upon acceptance, regardless of the Special Issue publication date.

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