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Currently, CDK inhibitors (CDKIs), particularly agents targeting CDK4\/6, have shown clinical activity in HR\n                    <jats:sup>+<\/jats:sup>\n                    \/HER\n                    <jats:sup>2\u2212<\/jats:sup>\n                    metastatic breast cancer. Recent structural elucidation of the CDK2 catalytic domain and its allosteric sites has enabled the development of several selective CDK2 inhibitors, many of which have exhibited encouraging antitumor activity. Moreover, emerging evidence further indicates that dual inhibition of CDK4\/6 and CDK2 can synergistically overcome resistance to CDK4\/6 blockade. Notably, recent studies have revealed that CDKIs can induce cellular senescence and enhance the efficacy of cancer immunotherapy. In this review, we outline the CDK family and their key functions in cell cycle control, summarize recent clinical advances in CDKI\u2010based therapies, with emphasis on CDK4\/6 and CDK2 inhibition, and discuss opportunities to integrate CDK\u2010targeted therapy with immunotherapy and other therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70442","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:44:56Z","timestamp":1772988296000},"page":"553-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cyclin\u2010dependent kinases as therapeutic targets in cancer: Recent advances, challenges, and opportunities"],"prefix":"10.1002","volume":"159","author":[{"given":"Ning","family":"Ju","sequence":"first","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology 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