Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies
Abstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and cell mitosis/division. They are validated targets for disease treatment, notably hematological cancers and solid tumors. Microtubule‐targeting agents (MTAs) exert t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | MedComm – Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mog2.46 |
| _version_ | 1797672753065623552 |
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| author | Xingyu Wang Benoît Gigant Xi Zheng Qiang Chen |
| author_facet | Xingyu Wang Benoît Gigant Xi Zheng Qiang Chen |
| author_sort | Xingyu Wang |
| collection | DOAJ |
| description | Abstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and cell mitosis/division. They are validated targets for disease treatment, notably hematological cancers and solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding cell proliferation, and promoting cell death. Recent advances in structural biology have unveiled novel perspectives for investigating multiple binding sites and mechanisms of action used by MTAs. In this review, we first provide an overview of the intricate structure and dynamics of microtubules. Then we explore the seven binding sites and the three primary strategies (stabilization, destabilization, and degradation) harnessed by MTAs. Furthermore, we introduce the emerging domain of microtubule‐targeting degraders, exemplified by PROteolysis TArgeting Chimeras and small‐molecule degraders, which enable precise degradation of specific microtubule‐associated proteins implicated in cancer pathogenesis. Additionally, we discuss the promising realm of precision‐targeted approaches, including antibody–drug conjugates and the utilization of photopharmacology in MTAs. Lastly, we provide a comprehensive overview of the clinical applications of microtubule‐targeting therapies, assessing their efficacy and current challenges. We aim to provide a global picture of MTAs development as well as insights into the microtubule‐targeting drug discovery for cancer treatment. |
| first_indexed | 2024-03-11T21:34:49Z |
| format | Article |
| id | doaj.art-6931313ccd3d49508ab1d7d7447abb7b |
| institution | Directory Open Access Journal |
| issn | 2769-6448 |
| language | English |
| last_indexed | 2024-03-11T21:34:49Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm – Oncology |
| spelling | doaj.art-6931313ccd3d49508ab1d7d7447abb7b2023-09-27T04:32:33ZengWileyMedComm – Oncology2769-64482023-09-0123n/an/a10.1002/mog2.46Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategiesXingyu Wang0Benoît Gigant1Xi Zheng2Qiang Chen3Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu ChinaUniversité Paris‐Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) Gif‐sur‐Yvette FranceDepartment of Thoracic Surgery West China Hospital, Sichuan University Chengdu ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu ChinaAbstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and cell mitosis/division. They are validated targets for disease treatment, notably hematological cancers and solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding cell proliferation, and promoting cell death. Recent advances in structural biology have unveiled novel perspectives for investigating multiple binding sites and mechanisms of action used by MTAs. In this review, we first provide an overview of the intricate structure and dynamics of microtubules. Then we explore the seven binding sites and the three primary strategies (stabilization, destabilization, and degradation) harnessed by MTAs. Furthermore, we introduce the emerging domain of microtubule‐targeting degraders, exemplified by PROteolysis TArgeting Chimeras and small‐molecule degraders, which enable precise degradation of specific microtubule‐associated proteins implicated in cancer pathogenesis. Additionally, we discuss the promising realm of precision‐targeted approaches, including antibody–drug conjugates and the utilization of photopharmacology in MTAs. Lastly, we provide a comprehensive overview of the clinical applications of microtubule‐targeting therapies, assessing their efficacy and current challenges. We aim to provide a global picture of MTAs development as well as insights into the microtubule‐targeting drug discovery for cancer treatment.https://doi.org/10.1002/mog2.46cancer therapymicrotubulemicrotubule‐targeting agentstubulintubulin‐targeting sites |
| spellingShingle | Xingyu Wang Benoît Gigant Xi Zheng Qiang Chen Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies MedComm – Oncology cancer therapy microtubule microtubule‐targeting agents tubulin tubulin‐targeting sites |
| title | Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies |
| title_full | Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies |
| title_fullStr | Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies |
| title_full_unstemmed | Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies |
| title_short | Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies |
| title_sort | microtubule targeting agents for cancer treatment seven binding sites and three strategies |
| topic | cancer therapy microtubule microtubule‐targeting agents tubulin tubulin‐targeting sites |
| url | https://doi.org/10.1002/mog2.46 |
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