Inhibiting CDK4/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences

Braal, C. Louwrens; Jongbloed, Elisabeth M; Wilting, Saskia M.; Mathijssen, Ron H.J.; Koolen, Stijn L.W.; Jager, Agnes

doi:10.1007/s40265-020-01461-2

Cited by 234 publications

(222 citation statements)

References 119 publications

(137 reference statements)

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“…Importantly, the NGP cell lines that possessed CDK4 amplification were sensitive to palbociclib, providing predictive importance of this genomic lesion [10]. In addition to palbociclib, ribociclib and abemaciclib, the other CDK4/6 inhibitors, have significantly prolonged the progression-free survival (PFS) of patients with advanced breast cancer [11]. As several clinical trials in other tumor types are ongoing, more information on predictive biomarkers for optimal treatment strategies for neuroblastomas will be made available in due course.…”

Section: Cdk4mentioning

confidence: 99%

Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

Ando

Nakagawara

2021

Biomolecules

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Unrestrained proliferation is a common feature of malignant neoplasms. Targeting the cell cycle is a therapeutic strategy to prevent unlimited cell division. Recently developed rationales for these selective inhibitors can be subdivided into two categories with antithetical functionality. One applies a “brake” to the cell cycle to halt cell proliferation, such as with inhibitors of cell cycle kinases. The other “accelerates” the cell cycle to initiate replication/mitotic catastrophe, such as with inhibitors of cell cycle checkpoint kinases. The fate of cell cycle progression or arrest is tightly regulated by the presence of tolerable or excessive DNA damage, respectively. This suggests that there is compatibility between inhibitors of DNA repair kinases, such as PARP inhibitors, and inhibitors of cell cycle checkpoint kinases. In the present review, we explore alterations to the cell cycle that are concomitant with altered DNA damage repair machinery in unfavorable neuroblastomas, with respect to their unique genomic and molecular features. We highlight the vulnerabilities of these alterations that are attributable to the features of each. Based on the assessment, we offer possible therapeutic approaches for personalized medicine, which are seemingly antithetical, but both are promising strategies for targeting the altered cell cycle in unfavorable neuroblastomas.

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Section: Cdk4mentioning

confidence: 99%

Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

Ando

Nakagawara

2021

Biomolecules

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“…Maximum concentration (C max ) is achieved within hours in all cases and the half-life within two days. Only for abemaciclib the saturation of drug absorption supported a twice-daily dosing regimen [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

“…Abemaciclib exerts less hematological toxicity, and it does not require dose interruptions, being gastrointestinal the most common dose-limiting toxicity [ 73 , 74 ]. Preclinical studies have shown that continuous administration of abemaciclib reduced tumor growth more efficiently compared with an intermittent schedule [ 72 ]. Abemaciclib also induces high senescence in BC cell lines.…”

Section: Discussionmentioning

confidence: 99%

The role of CDK4/6 inhibitors in early breast cancer

et al. 2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…According to the pivotal role of CDK4 and CDK6 in driving cell cycle progression through the G1 phase of the cell cycle, the most prominent effect of all CDK4/6i is the block of cell proliferation [ 41 ]. Biochemically, this cell cycle blockage is accompanied by the inhibition of Rb phosphorylation, an event that can be observed both in vitro and in vivo [ 41 , 49 ]. Therefore, it has been postulated that tumors with alteration in proteins regulating the progression through the G1 phase of the cell cycle will be the most sensitive to these inhibitors.…”

Section: Mechanism Of Action Of Cdk4/6 Inhibitorsmentioning

confidence: 99%

“… Information have been retrieved from [ 41 , 42 , 43 , 49 ]: Abbreviations: NR, Not Reported, nM, nanoMolar. …”

Section: Figurementioning

confidence: 99%

Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

Dall'Acqua

Bartoletti

Masoudi-Khoram

et al. 2021

Cancers

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Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

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Inhibiting CDK4/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences

Cited by 234 publications

References 119 publications

Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

The role of CDK4/6 inhibitors in early breast cancer

Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

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