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

Rossana RoncatoJacopo AngeliniArianna PaniErika CecchinAndrea Sartore-BianchiSalvatore SienaElena De MattiaFrancesco ScaglioneGiuseppe Toffoli
Published in: International journal of molecular sciences (2020)
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.
Keyphrases
  • metastatic breast cancer
  • cell cycle
  • oxidative stress
  • cell proliferation
  • risk assessment
  • combination therapy
  • smoking cessation
  • transcription factor
  • pi k akt
  • cell cycle arrest
  • genome wide analysis