Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015–2019)

2019 ◽  
Vol 29 (20) ◽  
pp. 126637 ◽  
Author(s):  
Concepción Sánchez-Martínez ◽  
María José Lallena ◽  
Sonia Gutiérrez Sanfeliciano ◽  
Alfonso de Dios
2015 ◽  
Vol 25 (17) ◽  
pp. 3420-3435 ◽  
Author(s):  
Concepción Sánchez-Martínez ◽  
Lawrence M. Gelbert ◽  
María José Lallena ◽  
Alfonso de Dios

ChemInform ◽  
2015 ◽  
Vol 46 (40) ◽  
pp. no-no ◽  
Author(s):  
Concepcion Sanchez-Martinez ◽  
Lawrence M. Gelbert ◽  
Maria Jose Lallena ◽  
Alfonso de Dios

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Habib Haybar ◽  
Mehhdi Shahrouzian ◽  
Zahra Gatavizadeh ◽  
Najmaldin Saki ◽  
Mahmood Maniati ◽  
...  

Objective: Cyclin D1 is an essential protein that acts as a mitogenic sensor. In this manuscript, we discuss the importance of cyclin D1 in oncology and cardio-oncology, and we challenge the prognostic and therapeutic response values of cyclin D1 to figure out if it can be a beneficial marker. We also discuss the agents and microRNAs that can be used as a potential therapeutic approach via regulating cyclin D1 expression in oncology and cardio-oncology. Discussion: Clinical significance of cyclin D1 is defined not only in several cancers such as breast cancer, melanoma, and glioblastoma but also in cardiomyocyte regeneration and cardiac hypertrophic growth. Several studies have indicated that the injection of cardiotoxic agents such as doxorubicin (DOX) induces damage to the cardiac system and increases cyclin D expression at single injection, which might be related to DXO-mediated damage in the adult heart. However, cyclin D1 overexpression leads to hypertrophic growth of cardiomyocytes, and cyclin-dependent kinase (CDK)) inhibitors such as p16 do not inhibit the hypertrophic growth of cardiomyocytes. Thus, the reaction is CDK-independent. Conclusions: Cyclin D1 overexpression is positively correlated with tumor progression, treatment response, cardiotoxicity, and poor prognosis. Cyclin D1 expression has an important role in cardiac hypertrophy, and it can be a promising marker in monitoring cardiomyocyte treatment responses, cardioprotection, and cardiotoxicity. Finally, cyclin D1 plays an important role in hypertrophic growth of cardiomyocytes via a novel mechanism. Given all these pieces of evidence, cyclin D1 can be introduced as a favorable biomarker in future cardiology and cardio-oncology.


2018 ◽  
Vol 53 (2) ◽  
pp. 195-203
Author(s):  
Keith A. Hecht ◽  
Christopher Selby

Objective: To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor–positive advanced breast cancer (ABC). Data Sources: A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. Study Selection and Data Extraction: Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. Data Synthesis: Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor–positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor–positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. Conclusions: The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.


2019 ◽  
Vol 50 (3) ◽  
pp. 261-270 ◽  
Author(s):  
Phuong Tran ◽  
Sang-Eun Lee ◽  
Dong-Hyun Kim ◽  
Yong-Chul Pyo ◽  
Jeong-Sook Park

2020 ◽  
Vol 12 (2) ◽  
pp. 127-145 ◽  
Author(s):  
Pingping Chen ◽  
Yinqiu Xu ◽  
Xuanyi Li ◽  
Hequan Yao ◽  
Kejiang Lin

Aim: CDK4/6 have critical roles in the early stage of the cell cycle. CDK2 acts later in the cell cycle and has a considerably broader range of protein substrates, some of which are essential for normal cell proliferation. Therefore, increasing the selectivity of cyclin-dependent kinase (CDK) inhibitors is critical. Methodology: In this study, we construct a versatile, specific CDK4 pharmacophore model that not only matches well with 8119 of the reported 9349 CDK4/6 inhibitors but also differentiates from the CDK2 pharmacophore. Results & Conclusion: we demonstrate the activity and selectivity determinants of CDK4/6 selective inhibitors based on the CDK4 pharmacophore model. Finally, we propose the future optimization strategy for CDK4/6 selective inhibitors, providing a theoretical basis for further research and development of CDK4/6 selective inhibitors.


2012 ◽  
Vol 133 (1) ◽  
pp. 26-39 ◽  
Author(s):  
Rene Kizek ◽  
Vojtech Adam ◽  
Jan Hrabeta ◽  
Tomas Eckschlager ◽  
Svatopluk Smutny ◽  
...  

2018 ◽  
Vol 10 (11) ◽  
pp. 1369-1388 ◽  
Author(s):  
Amy B Heptinstall ◽  
IWS Adiyasa ◽  
Céline Cano ◽  
Ian R Hardcastle

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