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Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and

Federica Villa1, Alessandra Crippa1, Davide Pelizzoni1

  • 1Medical Oncology, Oncology Department ASST Lecco, 23900 Lecco, Italy.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are common for metastatic breast cancer. This review explores resistance mechanisms and subsequent treatments for patients progressing on CDK4/6i therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are a standard first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer.
  • Acquired resistance to CDK4/6i is a significant clinical challenge, leading to disease progression.
  • There is a lack of established, guideline-recommended treatments for patients who progress on CDK4/6i therapy.

Purpose of the Study:

  • To review the cellular mechanisms of resistance to CDK4/6i in breast cancer.
  • To analyze potential therapeutic strategies for patients with acquired resistance to CDK4/6i.
  • To summarize clinical data on the efficacy of subsequent treatments following CDK4/6i therapy.

Main Methods:

  • Literature review of cellular resistance mechanisms to CDK4/6i.
  • Analysis of treatment strategies including hormonal therapy, targeted therapies (PI3K, mTOR, AKT inhibitors), and chemotherapy.
  • Review of clinical trial data for post-CDK4/6i therapies.

Main Results:

  • Resistance to CDK4/6i can be cell-cycle specific or non-specific, occurring as early or late progression.
  • Various therapeutic approaches are being investigated, including switching to other CDK4/6i, hormonal therapy, or targeted agents.
  • Clinical data on subsequent treatments show varying efficacy, highlighting the need for further research.

Conclusions:

  • Understanding resistance mechanisms is crucial for developing effective treatment strategies after CDK4/6i failure.
  • Subsequent treatment options for metastatic breast cancer progressing on CDK4/6i are evolving, with ongoing clinical trials.
  • Personalized treatment approaches based on resistance profiles may improve outcomes for patients with advanced breast cancer.
Keywords:
CDK 4/6 inhibitorscell-cycle-specific and non-specific resistancemetastatic breast cancer

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