| Naslov: | CDK4/6 inhibitors for breast cancer therapy—a review of clinical trials, structural and computational approaches |
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| Avtorji: | ID Avdičević, Adela (Avtor)
ID Lešnik, Samo (Avtor)
ID Bren, Urban (Avtor)
ID Čavka, Luka (Avtor) |
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| Datoteke: |  pharmaceuticals-19-00610-v2.pdf (6,93 MB)
MD5: 6F42476E8F44FCCDCAEE911465D50EEE
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| Jezik: | Angleški jezik |
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| Vrsta gradiva: | Članek v reviji |
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| Tipologija: | 1.02 - Pregledni znanstveni članek |
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| Organizacija: | FKKT - Fakulteta za kemijo in kemijsko tehnologijo
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| Opis: | Cyclin-dependent kinases 4 and 6 (CDK4/6) play a central role in the regulation of cell cycle progression and represent important therapeutic targets in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer. The introduction of selective CDK4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, in combination with endocrine therapy, has significantly improved clinical outcomes and has become a standard treatment strategy in both metastatic and high-risk early-stage disease. Nevertheless, treatment resistance and disease progression remain major clinical challenges. A deeper understanding of the structural characteristics of CDK4/6 and the molecular basis of inhibitor binding is therefore essential for improving therapeutic strategies and guiding the development of new targeted agents. This review provides an integrated overview of the structural features of CDK4/6 and their role in cell cycle regulation, summarizes the clinical development and major clinical trials of currently approved CDK4/6 inhibitors, and discusses recent computational studies investigating inhibitor binding and conformational dynamics. Particular attention is given to the application of in silico approaches, including molecular docking, molecular dynamics simulations, and binding free-energy calculations, which provide insights into mechanisms of therapy resistance and potential strategies to overcome them and support the identification and optimization of novel CDK4/6-targeted therapeutic candidates. By integrating structural, clinical, and computational perspectives, this review highlights current knowledge and emerging directions in CDK4/6 research that may advance the development of more personalized therapies for HR+/HER2− breast cancer, while accounting for both intrinsic and de novo resistance mechanisms. |
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| Ključne besede: | CDK4/6, abemaciclib, palbociclib, ribociclib, molecular dynamic simulations, drug resistance |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Poslano v recenzijo: | 06.03.2026 |
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| Datum sprejetja članka: | 08.04.2026 |
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| Datum objave: | 10.04.2026 |
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| Založnik: | MDPI |
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| Leto izida: | 2026 |
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| Št. strani: | 47 str. |
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| Številčenje: | Vol. 19, iss. 4, [article no.] 610 |
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| PID: | 20.500.12556/DKUM-97968  |
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| UDK: | 615.3 |
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| COBISS.SI-ID: | 276994051 |
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| DOI: | 10.3390/ph19040610 |
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| ISSN pri članku: | 1424-8247 |
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| Avtorske pravice: | © 2026 by the authors |
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| Datum objave v DKUM: | 05.05.2026 |
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| Število ogledov: | 155 |
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| Število prenosov: | 13 |
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| Metapodatki: |    |
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| Področja: | Ostalo
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