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Biomedicines
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Metal-Based Complexes in Cancer Treatment
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Metal-Based Complexes in Cancer Treatment

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 46608

Special Issue Editors

Dr. Tania Gamberi

E-Mail Website
Guest Editor
Department of Clinical and Preclinical Biomedical Sciences, University of Florence, Florence, Italy
Interests: gold-based anticancer drugs; auranofin; thioredoxin reductase; ovarian cancer; cancer cell metabolism; proteomics; redox proteomics
Dr. Muhammad Hanif

E-Mail Website
Co-Guest Editor
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Interests: anticancer agents; metals in medicine; Medicinal bioinorganic chemistry; drug delivery; antibacterial agents; metal complexes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metal-based complexes contribute a vital part in the available arsenal of cytotoxic agents today. Platinum(II) complexes, specifically targeting genomic DNA (e.g., cisplatin and carboplatin), are widely used in the clinic for the treatment of various cancers. Nearly 50% of cancer patients, who undergo chemotherapy, receive a platinum drug either alone or in combination therapy. Despite their central role in cancer chemotherapy, platinum drugs suffer serious drawbacks such as the limited spectrum of antitumor activities, systemic dose-related toxicity, and the frequent induction of drug resistance, often leading to treatment failure. These observations have prompted a strong interest in the investigation of nonplatinum metal-based drugs as an effective alternative. Several other platinum and nonplatinum metal complexes (e.g., Ti, Pd, Ru, Au) have shown potent cytotoxic and antitumor effects. Unlike to platinum drugs, these are often relying on DNA-independent biochemical mechanisms such as targeting tumor-associated proteins and induction of immunogenic antitumor properties for their therapeutic effects. Notably, a few of these drugs are already in clinical trials, and several are awaiting ethical approval to enter the trial phase. This Special Issue will include original research and review articles on the use of platinum and nonplatinum metal complexes in cancer therapy. In particular, papers focusing on the design and developing targeted metal-based anticancer agents, understanding their mechanisms of action, and innovative drug delivery approaches will be considered. Topics of interest for this Special Issue include but are not limited to the following:

  • medicinal chemistry of metal-based anticancer drugs;
  • synthesis/improvement of platinum and nonplatinum metal complexes;
  • mechanisms of action/biological targets of metal-based drugs;
  • clinical applications of metal-based anticancer agents;
  • uptake, toxicity, and resistance of metal-based anticancer agents;
  • metal-based complexes in targeted drug delivery;
  • metal-based drugs in cancer combinatorial therapy

Dr. Tania Gamberi
Dr. Muhammad Hanif
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • metal-based anticancer drugs
  • platinum and nonplatinum metal complexes
  • mechanisms of action/biological targets of metal-based drugs
  • clinical applications of metal-based anticancer agents
  • cellular uptake, toxicity, and resistance of metal-based anticancer agents
  • targeted drug delivery of metal-based compounds
  • metal-based drugs in cancer combinatorial therapy

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Published Papers (11 papers)

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Editorial

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3 pages, 186 KiB  
Editorial
Metal-Based Complexes in Cancer Treatment
by Tania Gamberi and Muhammad Hanif
Biomedicines 2022, 10(10), 2573; https://doi.org/10.3390/biomedicines10102573 - 14 Oct 2022
Cited by 14 | Viewed by 2281
Abstract
Metal-based complexes contribute a vital part to the available arsenal of cytotoxic agents today [...] Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)

Research

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11 pages, 1177 KiB  
Article
Early and Long-Term Ototoxicity Noted in Children Due to Platinum Compounds: Prevalence and Risk Factors
by Alberto Romano, Serena Rivetti, Francesca Brigato, Stefano Mastrangelo, Giorgio Attinà, Palma Maurizi, Jacopo Galli, Anna Rita Fetoni and Antonio Ruggiero
Biomedicines 2023, 11(2), 261; https://doi.org/10.3390/biomedicines11020261 - 18 Jan 2023
Cited by 7 | Viewed by 1977
Abstract
Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and [...] Read more.
Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression. Methods: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities. Results: At the end of the treatment, 17 patients (32.08%) presented ototoxicity, according to the Boston SIOP Ototoxicity Scale; the risk factors included a higher serum creatinine value at diagnosis, having undergone cranial radiotherapy, and needing magnesium supplementation. After 5 years from the end of the treatment, the number of patients with exhibiting ototoxicity was 31 (58.5%); the factors that influenced the onset/progression of the damage were having undergone radiotherapy (HR 1.23; p < 0.01) and having received therapy with aminoglycosides (HR 1.27; p < 0.01). Conclusions: Ototoxicity caused by platinum compounds can occur even after the conclusion of the treatments, and the factors affecting its progression are radiotherapy and the aminoglycosides therapy. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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18 pages, 8352 KiB  
Article
Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes
by Kirill K. Geyl, Sergey V. Baykov, Stanislav A. Kalinin, Alexandr S. Bunev, Marina A. Troshina, Tatiana V. Sharonova, Mikhail Yu. Skripkin, Svetlana O. Kasatkina, Sofia I. Presnukhina, Anton A. Shetnev, Mikhail Yu. Krasavin and Vadim P. Boyarskiy
Biomedicines 2022, 10(2), 461; https://doi.org/10.3390/biomedicines10020461 - 16 Feb 2022
Cited by 12 | Viewed by 3289
Abstract
Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two [...] Read more.
Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)2Cl]+[Cl]− or (Cu(L)2Cl2) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCI-H1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity. Two nitro-group substituted complexes Cu(U3)2Cl2 (IC50 = 39.6 ± 4.5 μM) and Cu(U11)2Cl2 (IC50 = 33.4 ± 3.8 μM) demonstrate enhanced activity against the drug resistant NCI-H1975 cells with moderate selectivity toward normal WI-26 VA4 cells. The antiproliferative mechanism of cell death underlying the growth inhibitory effect of the synthesized complexes was studied via additional experiments, including the cell cycle analysis and the apoptosis induction test. Reassuringly, certain 2-pyridyl urea-based Cu(II) complexes exerted cell line-specific antiproliferative effect which renders them valuable starting points for further unveiling the anticancer potential of this class of coordination compounds. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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20 pages, 5014 KiB  
Article
Pd2Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice
by Martin Vojtek, Salomé Gonçalves-Monteiro, Patrícia Šeminská, Katarína Valová, Loreto Bellón, Patrícia Dias-Pereira, Franklim Marques, Maria P. M. Marques, Ana L. M. Batista de Carvalho, Helder Mota-Filipe, Isabel M. P. L. V. O. Ferreira and Carmen Diniz
Biomedicines 2022, 10(2), 210; https://doi.org/10.3390/biomedicines10020210 - 19 Jan 2022
Cited by 8 | Viewed by 2943
Abstract
Pd2Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd2 [...] Read more.
Pd2Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd2Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd2Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd2Spm was observed in MDA-MB-231 cells (IC50 values of 7.3–8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5–228.9 µM). Pd2Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd2Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd2Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd2Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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20 pages, 2885 KiB  
Article
In Vitro Nephrotoxicity Studies of Established and Experimental Platinum-Based Compounds
by Sarah Schoch, Vasily Sen, Walburgis Brenner, Andrea Hartwig and Beate Köberle
Biomedicines 2021, 9(8), 1033; https://doi.org/10.3390/biomedicines9081033 - 18 Aug 2021
Cited by 9 | Viewed by 3432
Abstract
Cisplatin is one of the most commonly used drugs for the treatment of various solid cancers. However, its efficacy is restricted by severe side effects, especially dose-limiting nephrotoxicity. New platinum-based compounds are designed to overcome this limitation. Previous investigations showed that the platinum(IV)–nitroxyl [...] Read more.
Cisplatin is one of the most commonly used drugs for the treatment of various solid cancers. However, its efficacy is restricted by severe side effects, especially dose-limiting nephrotoxicity. New platinum-based compounds are designed to overcome this limitation. Previous investigations showed that the platinum(IV)–nitroxyl complex PN149 is highly cytotoxic in various tumor cell lines. In the present study, investigations with PN149 were extended to normal human kidney tubule epithelia. Coincident with higher intracellular platinum accumulation, the cytotoxicity of PN149 in the proximal tubule epithelial cell line ciPTEC was more pronounced compared to the established platinum chemotherapeutics cisplatin, carboplatin and oxaliplatin. Quantitative gene expression profiling revealed the induction of ROS-inducible and anti-oxidative genes, suggesting an oxidative stress response by PN149. However, in contrast to cisplatin, no pro-inflammatory response was observed. Genes coding for distinct DNA damage response factors and genes related to apoptosis were up-regulated, indicating the activation of the DNA damage response system and induction of the apoptotic cascade by PN149. Altogether, a comparable transcriptional response was observed for PN149 and the platinum chemotherapeutics. However, the lack of inflammatory activity, which is a possible cause contributing to toxicity in human renal proximal tubule epithelia, might indicate the reduced nephrotoxic potential of PN149. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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18 pages, 2559 KiB  
Article
Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells
by Giulia Gorini, Francesca Magherini, Tania Fiaschi, Lara Massai, Matteo Becatti, Alessandra Modesti, Luigi Messori and Tania Gamberi
Biomedicines 2021, 9(8), 871; https://doi.org/10.3390/biomedicines9080871 - 23 Jul 2021
Cited by 14 | Viewed by 2889
Abstract
Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in [...] Read more.
Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, disruption of the cell redox balance, impairment of the mitochondrial membrane potential, and induction of associated metabolic changes. In addition, evidence was gained of the remarkable contribution of ASK1 (apoptosis-signal-regulating kinase-1) and AKT pathways to gold(III)-induced apoptotic signaling. Overall, the observed effects may be traced back to gold(III) reduction and subsequent formation and release of gold(I) species that are able to bind and inhibit several enzymes responsible for the intracellular redox homeostasis, in particular the selenoenzyme thioredoxin reductase. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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21 pages, 5599 KiB  
Article
Noble Metals for Modern Implant Materials: MOCVD of Film Structures and Cytotoxical, Antibacterial, and Histological Studies
by Svetlana I. Dorovskikh, Evgeniia S. Vikulova, Elena V. Chepeleva, Maria B. Vasilieva, Dmitriy A. Nasimov, Eugene A. Maksimovskii, Alphiya R. Tsygankova, Tamara V. Basova, David S. Sergeevichev and Natalya B. Morozova
Biomedicines 2021, 9(8), 851; https://doi.org/10.3390/biomedicines9080851 - 21 Jul 2021
Cited by 11 | Viewed by 2925
Abstract
This work is aimed at developing the modification of the surface of medical implants with film materials based on noble metals in order to improve their biological characteristics. Gas-phase transportation methods were proposed to obtain such materials. To determine the effect of the [...] Read more.
This work is aimed at developing the modification of the surface of medical implants with film materials based on noble metals in order to improve their biological characteristics. Gas-phase transportation methods were proposed to obtain such materials. To determine the effect of the material of the bottom layer of heterometallic structures, Ir, Pt, and PtIr coatings with a thickness of 1.4–1.5 μm were deposited by metal–organic chemical vapor deposition (MOCVD) on Ti6Al4V alloy discs. Two types of antibacterial components, namely, gold nanoparticles (AuNPs) and discontinuous Ag coatings, were deposited on the surface of these coatings. AuNPs (11–14 nm) were deposited by a pulsed MOCVD method, while Ag films (35–40 nm in thickness) were obtained by physical vapor deposition (PVD). The cytotoxic (24 h and 48 h, toward peripheral blood mononuclear cells (PBMCs)) and antibacterial (24 h) properties of monophase (Ag, Ir, Pt, and PtIr) and heterophase (Ag/Pt, Ag/Ir, Ag/PtIr, Au/Pt, Au/Ir, and Au/PtIr) film materials deposited on Ti-alloy samples were studied in vitro and compared with those of uncoated Ti-alloy samples. Studies of the cytokine production by PBMCs in response to incubation of the samples for 24 and 48 h and histological studies at 1 and 3 months after subcutaneous implantation in rats were also performed. Despite the comparable thickness of the fibrous capsule after 3 months, a faster completion of the active phase of encapsulation was observed for the coated implants compared to the Ti alloy analogs. For the Ag-containing samples, growth inhibition of S. epidermidis, S. aureus, Str. pyogenes, P. aeruginosa, and Ent. faecium was observed. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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18 pages, 3829 KiB  
Article
High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes
by Md. Salman Shakil, Shahida Parveen, Zohaib Rana, Fearghal Walsh, Sanam Movassaghi, Tilo Söhnel, Mayur Azam, Muhammad Ashraf Shaheen, Stephen M. F. Jamieson, Muhammad Hanif, Rhonda J. Rosengren and Christian G. Hartinger
Biomedicines 2021, 9(2), 123; https://doi.org/10.3390/biomedicines9020123 - 27 Jan 2021
Cited by 10 | Viewed by 4444
Abstract
Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a–1c and 3-hydroxy-4-thiopyridones 1d–1f as well as their Ru(η6-p-cymene)Cl complexes 2a–2f [...] Read more.
Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a–1c and 3-hydroxy-4-thiopyridones 1d–1f as well as their Ru(η6-p-cymene)Cl complexes 2a–2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d–1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low μM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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Review

Jump to: Editorial, Research

32 pages, 2691 KiB  
Review
Photoactive and Luminescent Transition Metal Complexes as Anticancer Agents: A Guiding Light in the Search for New and Improved Cancer Treatments
by Brondwyn S. McGhie and Janice R. Aldrich-Wright
Biomedicines 2022, 10(3), 578; https://doi.org/10.3390/biomedicines10030578 - 1 Mar 2022
Cited by 24 | Viewed by 4444
Abstract
Cancer continues to be responsible for the deaths of more than 9 million people worldwide each year. Current treatment options are diverse, but low success rates, particularly for those with late-stage cancers, continue to be a problem for clinicians and their patients. The [...] Read more.
Cancer continues to be responsible for the deaths of more than 9 million people worldwide each year. Current treatment options are diverse, but low success rates, particularly for those with late-stage cancers, continue to be a problem for clinicians and their patients. The effort by researchers globally to find alternative treatment options is ongoing. In the present study, we focused on innovations in inorganic anticancer therapies, specifically those with photoactive and luminescent properties. Transition metals offer distinct advantages compared to wholly organic compounds in both chemotherapeutics and luminescence properties. Here we report on the characteristics that result from discrete structural changes that have been expertly used to fine-tune their properties, and how diverse inherent luminescent properties have been widely employed to monitor cellular localization to photodynamic therapy. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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46 pages, 9873 KiB  
Review
Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance
by Maria V. Babak and Dohyun Ahn
Biomedicines 2021, 9(8), 852; https://doi.org/10.3390/biomedicines9080852 - 21 Jul 2021
Cited by 135 | Viewed by 8622
Abstract
Copper (Cu) is a vital element required for cellular growth and development; however, even slight changes in its homeostasis might lead to severe toxicity and deleterious medical conditions. Cancer patients are typically associated with higher Cu content in serum and tumor tissues, indicating [...] Read more.
Copper (Cu) is a vital element required for cellular growth and development; however, even slight changes in its homeostasis might lead to severe toxicity and deleterious medical conditions. Cancer patients are typically associated with higher Cu content in serum and tumor tissues, indicating increased demand of cancer cells for this micronutrient. Cu is known to readily cycle between the +1 and +2 oxidation state in biological systems. The mechanism of action of Cu complexes is typically based on their redox activity and induction of reactive oxygen species (ROS), leading to deadly oxidative stress. However, there are a number of other biomolecular mechanisms beyond ROS generation that contribute to the activity of anticancer Cu drug candidates. In this review, we discuss how interfering with intracellular Cu balance via either diet modification or addition of inorganic Cu supplements or Cu-modulating compounds affects tumor development, progression, and sensitivity to treatment modalities. We aim to provide the rationale for the use of Cu-depleting and Cu-overloading conditions to generate the best possible patient outcome with minimal toxicity. We also discuss the advantages of the use of pre-formed Cu complexes, such as Cu-(bis)thiosemicarbazones or Cu-N-heterocyclic thiosemicarbazones, in comparison with the in situ formed Cu complexes with metal-binding ligands. In this review, we summarize available clinical and mechanistic data on clinically relevant anticancer drug candidates, including Cu supplements, Cu chelators, Cu ionophores, and Cu complexes. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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20 pages, 2490 KiB  
Review
Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments
by Damiano Cirri, Francesco Bartoli, Alessandro Pratesi, Emma Baglini, Elisabetta Barresi and Tiziano Marzo
Biomedicines 2021, 9(5), 504; https://doi.org/10.3390/biomedicines9050504 - 4 May 2021
Cited by 52 | Viewed by 5932
Abstract
This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic [...] Read more.
This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments. Full article
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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