{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:10:01Z","timestamp":1788775801352,"version":"build-2803163510"},"reference-count":195,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Research Project of Hunan Provincial Health Commission","award":["20254740"],"award-info":[{"award-number":["20254740"]}]},{"award":["20254740"],"award-info":[{"award-number":["20254740"]}],"id":[{"id":"https:\/\/ror.org\/059qgvg50","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific Research Fund of Hunan Provincial Education Department","award":["25B0968"],"award-info":[{"award-number":["25B0968"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Drug resistance in cancer remains a major barrier to durable therapeutic benefits and limits the effectiveness of chemotherapy, targeted therapy, and combination treatment in multiple malignancies. Increasing evidence indicates that specific kinesin superfamily proteins contribute to tumor adaptation and therapeutic response in a context-dependent manner through their roles in mitotic regulation, intracellular transport, and stress-response pathways. Aberrant expression of multiple kinesin family members has been documented across diverse cancers and is frequently associated with aggressive clinicopathological features, poor prognosis, and resistance to treatment. However, expression alterations alone do not establish functional dependency, and mechanistic validation is required to distinguish true resistance drivers from adaptive tumor states. In this review, we summarize the classification, biological functions, and abnormal expression patterns of kinesins in cancer; discuss the major mechanisms through which they contribute to drug resistance; and examine strategies for targeting kinesins, including natural-product-derived direct inhibitors, small-molecule inhibitor development, rational combination approaches, and structure-guided and computational optimization strategies. We also evaluate the biomarker potential of kinesin dysregulation and the value of advanced preclinical models for mechanistic and translational investigations. Finally, we highlight the major challenges that hinder clinical translation, including target specificity, compensatory resistance, insufficient biomarker validation, and tumor heterogeneity. Future progress will require integration of functional genomics, multiomics profiling, and mechanism-guided therapeutic strategies to determine when kinesin inhibition represents a clinically actionable approach for resistant malignancies.<\/jats:p>","DOI":"10.3390\/cancers18172872","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kinesins in Cancer Drug Resistance: Mechanisms, Therapeutic Targeting, and Translational Potential"],"prefix":"10.3390","volume":"18","author":[{"given":"Yayun","family":"Tan","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Hunan University of Medicine General Hospital, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Hunan University of Medicine General Hospital, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3365-0379","authenticated-orcid":false,"given":"Zhizhong","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102818","DOI":"10.1016\/j.jbc.2022.102818","article-title":"Positive charge in the K-loop of the kinesin-3 motor KIF1A regulates superprocessivity by enhancing microtubule affinity in the one-head-bound state","volume":"299","author":"Zaniewski","year":"2023","journal-title":"J. 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