CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions.

Abstract

Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use.

• Authors: Rossana Roncato, Jacopo Angelini, Arianna Pani, Erika Cecchin, Andrea Sartore-Bianchi, Salvatore Siena, Elena De Mattia, Francesco Scaglione, Giuseppe Toffoli
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 17 (Sep 01 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32883002 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Animals
• Breast Neoplasms (drug therapy, enzymology, genetics, pathology)
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors, genetics)
• Cyclin-Dependent Kinase 6 (antagonists & inhibitors, genetics)
• Female
• Humans
• Molecular Targeted Therapy
• Protein Kinase Inhibitors (therapeutic use)