Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy
Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/888 |
| _version_ | 1797410577535991808 |
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| author | Shota Yamamoto Nobuaki Egashira |
| author_facet | Shota Yamamoto Nobuaki Egashira |
| author_sort | Shota Yamamoto |
| collection | DOAJ |
| description | Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxidative stress, and alterations of transcriptional programs in both the peripheral and central nervous systems. Moreover, we describe the necessity of advancing studies that identify the potential efficacy of approved drugs on the basis of pathological mechanisms, as this is a convincing strategy for rapid translation to patients with cancer and BIPN. |
| first_indexed | 2024-03-09T04:31:05Z |
| format | Article |
| id | doaj.art-adb2ffd8c437402790213e4cd6ae75c4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:31:05Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-adb2ffd8c437402790213e4cd6ae75c42023-12-03T13:35:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122288810.3390/ijms22020888Pathological Mechanisms of Bortezomib-Induced Peripheral NeuropathyShota Yamamoto0Nobuaki Egashira1Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo 162-8655, JapanDepartment of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, JapanBortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxidative stress, and alterations of transcriptional programs in both the peripheral and central nervous systems. Moreover, we describe the necessity of advancing studies that identify the potential efficacy of approved drugs on the basis of pathological mechanisms, as this is a convincing strategy for rapid translation to patients with cancer and BIPN.https://www.mdpi.com/1422-0067/22/2/888bortezomibperipheral neuropathyneurotoxicityneuropathic paindrug repositioningdrug repurposing |
| spellingShingle | Shota Yamamoto Nobuaki Egashira Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy International Journal of Molecular Sciences bortezomib peripheral neuropathy neurotoxicity neuropathic pain drug repositioning drug repurposing |
| title | Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy |
| title_full | Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy |
| title_fullStr | Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy |
| title_full_unstemmed | Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy |
| title_short | Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy |
| title_sort | pathological mechanisms of bortezomib induced peripheral neuropathy |
| topic | bortezomib peripheral neuropathy neurotoxicity neuropathic pain drug repositioning drug repurposing |
| url | https://www.mdpi.com/1422-0067/22/2/888 |
| work_keys_str_mv | AT shotayamamoto pathologicalmechanismsofbortezomibinducedperipheralneuropathy AT nobuakiegashira pathologicalmechanismsofbortezomibinducedperipheralneuropathy |