Prevention of anticancer therapy-induced neurotoxicity: Putting DNA damage in perspective

Brinkmann, Vanessa; Fritz, Gerhard

doi:10.1016/j.neuro.2022.04.009

Cited by 3 publications

(3 citation statements)

References 119 publications

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“…This debilitating condition often presents in a ‘socks and gloves’ manner due to drug-induced neurotoxicity in the sensory neurons of dorsal root ganglia, such that the feet and hands are affected by pain and numbness [ 137 , 138 , 139 ]. Complicating our understanding of CIPN, and developing treatments for CIPN, is that different antineoplastic agents used for specific cancers have different mechanisms of action [ 140 , 141 ]. Although molecular mechanisms of CIPN are incompletely understood, common pathogenic mechanisms include altered calcium homeostasis and mitochondrial dysfunction [ 140 ], two parameters for which GEFBs have been characterised ( Table 2 ).…”

Section: Leveraging Gefb and Ipsc Technologies For Pre-clinical Appli...mentioning

confidence: 99%

Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs

Stellon

Talbot

Hewitt

et al. 2023

IJMS

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Neurodegenerative diseases present a progressive loss of neuronal structure and function, leading to cell death and irrecoverable brain atrophy. Most have disease-modifying therapies, in part because the mechanisms of neurodegeneration are yet to be defined, preventing the development of targeted therapies. To overcome this, there is a need for tools that enable a quantitative assessment of how cellular mechanisms and diverse environmental conditions contribute to disease. One such tool is genetically encodable fluorescent biosensors (GEFBs), engineered constructs encoding proteins with novel functions capable of sensing spatiotemporal changes in specific pathways, enzyme functions, or metabolite levels. GEFB technology therefore presents a plethora of unique sensing capabilities that, when coupled with induced pluripotent stem cells (iPSCs), present a powerful tool for exploring disease mechanisms and identifying novel therapeutics. In this review, we discuss different GEFBs relevant to neurodegenerative disease and how they can be used with iPSCs to illuminate unresolved questions about causes and risks for neurodegenerative disease.

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Section: Leveraging Gefb and Ipsc Technologies For Pre-clinical Appli...mentioning

confidence: 99%

Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs

Stellon

Talbot

Hewitt

et al. 2023

IJMS

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“…Many anti-cancer drugs have been reported to cause side effects such as oral mucositis, neurotoxicity, and extravasation (leak of intravenously injected drugs and fluids out of the blood vessels) in clinical practice [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Oral mucositis not only reduces the patient’s quality of life due to accompanying pain, but lowers oral intake, therefore causing dehydration, and can trigger systemic bacterial infection and invasion.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, there are currently no established prevention or treatment methods for oral mucositis [ 1 , 2 , 3 ]. Even if the drugs were withdrawn, the induced peripheral neuropathy may leave rare recovery and lifelong disability [ 4 , 5 , 6 ]. Extravasation is more likely to occur when the peripheral venous wall is fragile or when phlebitis occurs, leading to the constriction and clogging of blood vessels, and then inflammation and necrosis [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

et al. 2023

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Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

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Synthesis and biological properties of small molecules — ligands of non-canonical DNA and RNA structures

Abramovich,

Zaikina,

Barskaya

et al. 2024

RUSS CHEM REV

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Nucleic acids are important targets for many anticancer drugs. Apart from the canonical B-DNA double helix, DNA forms a number of non-canonical structures (G-quadruplexes, i-motifs, hairpins, triplexes, etc.), which play an important role in the regulation of biological processes. Binding to non-canonical DNA structures occurs mainly by π–π-stacking. Therefore, aromatic and heteroaromatic compounds, in particular fused poly-aromatic compounds (acridines, anthraquinones, carbazoles), porphyrins, benzothiazoles, benzimidazoles, pyridines, and quinolines, as well as their complexes are used as ligands for secondary structures. These ligands should possess not only high selectivity to non-canonical structures compared to double-stranded DNA, but also relatively high solubility and penetration through cell membranes. This review summarizes the achievements of 2020–2024 in the synthesis and biological studies of (hetero)arenes (acridines, anthraquinones, benzazoles, xanthones, porphyrins) and coordination compounds that have exhibited anticancer activity as a result of binding to non-canonical DNA or RNA structures. Ligands of various types of non-canonical nucleic acid structures (G-quadruplexes, i-motifs, triplexes, hairpins) are considered and their cytotoxic activity and structure–property relationships are compared. <br> The bibliography includes 166 references.

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Prevention of anticancer therapy-induced neurotoxicity: Putting DNA damage in perspective

Cited by 3 publications

References 119 publications

Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs

Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

Synthesis and biological properties of small molecules — ligands of non-canonical DNA and RNA structures

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