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Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines. The molecular mechanisms of CIPN have not been fully understood. H...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796379/ https://www.ncbi.nlm.nih.gov/pubmed/33396481 http://dx.doi.org/10.3390/ijms22010367 |
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author | Sekiguchi, Fumiko Kawabata, Atsufumi |
author_facet | Sekiguchi, Fumiko Kawabata, Atsufumi |
author_sort | Sekiguchi, Fumiko |
collection | PubMed |
description | Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines. The molecular mechanisms of CIPN have not been fully understood. High mobility group box 1 (HMGB1), a nuclear protein, is a damage-associated molecular pattern protein now considered to function as a pro-nociceptive mediator once released to the extracellular space. Most interestingly, HMGB1 plays a key role in the development of CIPN. Soluble thrombomodulin (TMα), known to degrade HMGB1 in a thrombin-dependent manner, prevents CIPN in rodents treated with paclitaxel, oxaliplatin, or vincristine and in patients with colorectal cancer undergoing oxaliplatin-based chemotherapy. In this review, we describe the role of HMGB1 and its upstream/downstream mechanisms in the development of CIPN and show drug candidates that inhibit the HMGB1 pathway, possibly useful for prevention of CIPN. |
format | Online Article Text |
id | pubmed-7796379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77963792021-01-10 Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy Sekiguchi, Fumiko Kawabata, Atsufumi Int J Mol Sci Review Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines. The molecular mechanisms of CIPN have not been fully understood. High mobility group box 1 (HMGB1), a nuclear protein, is a damage-associated molecular pattern protein now considered to function as a pro-nociceptive mediator once released to the extracellular space. Most interestingly, HMGB1 plays a key role in the development of CIPN. Soluble thrombomodulin (TMα), known to degrade HMGB1 in a thrombin-dependent manner, prevents CIPN in rodents treated with paclitaxel, oxaliplatin, or vincristine and in patients with colorectal cancer undergoing oxaliplatin-based chemotherapy. In this review, we describe the role of HMGB1 and its upstream/downstream mechanisms in the development of CIPN and show drug candidates that inhibit the HMGB1 pathway, possibly useful for prevention of CIPN. MDPI 2020-12-31 /pmc/articles/PMC7796379/ /pubmed/33396481 http://dx.doi.org/10.3390/ijms22010367 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sekiguchi, Fumiko Kawabata, Atsufumi Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title | Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title_full | Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title_fullStr | Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title_full_unstemmed | Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title_short | Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy |
title_sort | role of hmgb1 in chemotherapy-induced peripheral neuropathy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796379/ https://www.ncbi.nlm.nih.gov/pubmed/33396481 http://dx.doi.org/10.3390/ijms22010367 |
work_keys_str_mv | AT sekiguchifumiko roleofhmgb1inchemotherapyinducedperipheralneuropathy AT kawabataatsufumi roleofhmgb1inchemotherapyinducedperipheralneuropathy |