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How to Treat HR+/HER2- Metastatic Breast Cancer Patients after CDK4/6 Inhibitors: An Unfinished Story.

Viola CogliatiSerena CapiciFrancesca Fulvia PepePierluigi di MauroFrancesca RivaFederica CicchielloClaudia MaggioniNicoletta CordaniMaria Grazia CerritoMarina Elena Cazzaniga
Published in: Life (Basel, Switzerland) (2022)
CDK4/6 inhibitors in association with endocrine therapy represent the best therapeutic choice for either endocrine-sensitive or resistant hormone-receptor-positive advanced breast cancer patients. On the contrary, the optimal therapeutic strategy after the failure of CDK4/6 inhibitors-based treatment still remains an open question worldwide. In this review, we analyze the most studied mechanisms of resistance to CDK4/6 inhibitors treatment, as well as the most significant results of retrospective and prospective trials in the setting of progression after CDK4/6 inhibitors, to provide the reader a comprehensive overview from both a preclinical and especially a clinical perspective. In our opinion, an approach based on a deeper knowledge of resistance mechanisms to CDK4/6 inhibitors, but also on a careful analysis of what is done in clinical practice, can lead to a better definition of prospective randomized trials, to implement a personalized sequence approach, based on molecular analyses.
Keyphrases
  • cell cycle
  • clinical practice
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  • squamous cell carcinoma
  • cross sectional
  • cell proliferation
  • mesenchymal stem cells
  • combination therapy
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  • amino acid
  • decision making