Rhenium‐Based Complexes and in Vivo Testing: A Brief History

Capper, Miles S.; Packman, Hollie; Rehkämper, Mark

doi:10.1002/cbic.202000117

Cited by 43 publications

(35 citation statements)

References 31 publications

(93 reference statements)

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“…In addition to the compounds ready for clinical appliance, to date numerous Ru-based derivatives, both inorganic and organic, have been investigated throughout advanced preclinical phase [ 85 , 87 , 123 ]. Indeed, several ruthenium complexes with attractive physico-chemical and biochemical properties, including superior anticancer activity, have been intensively studied as promising candidates within the frame of a prospective “ruthenotherapy” [ 124 , 125 ].…”

Section: Ru-based Drugs Upgrading For Cancer Treatments: Advancemementioning

confidence: 99%

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Ferraro

Piccolo

Misso

et al. 2020

Cells

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In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

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Section: Ru-based Drugs Upgrading For Cancer Treatments: Advancemementioning

confidence: 99%

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Ferraro

Piccolo

Misso

et al. 2020

Cells

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“…Attempts to substitute platinum with other metals has not produced tangible results in a clinical setting. Among all metal-based drugs, those containing rhenium have recently attracted major interest: several rhenium-based compounds have been tested for their anticancer activity in vitro and in vivo with promising results [3,8,9,24,46]. However, the lack of a known mechanism of action and molecular target represents a major obstacle in advancing these therapeutics to the clinical trial stage.…”

Section: Discussionmentioning

confidence: 99%

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Domenichini

Casari

Simpson

et al. 2020

J Exp Clin Cancer Res

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Background Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies. Methods Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds. Results We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts. Conclusions Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

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“…Attempts to substitute platinum with other metals has not produced tangible results in a clinical setting. Among all metal-based drugs, those containing rhenium have recently attracted major interest: several rhenium-based compounds have been tested for their anticancer activity in vitro and in vivo with promising results (24,(46)(47)(48)(49). However, the lack of a known mechanism of action and molecular target represents a major obstacle in advancing these therapeutics to the clinical trial stage.…”

Section: Discussionmentioning

confidence: 99%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

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Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

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Rhenium‐Based Complexes and in Vivo Testing: A Brief History

Cited by 43 publications

References 31 publications

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

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