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Updated: Oct 20, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

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Published on: May 14, 2016

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Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor

Kevin Freeman-Cook1, Robert L Hoffman1, Nichol Miller1

  • 1Pfizer Global Research and Development La Jolla, 10770 Science Center Drive, San Diego, CA 92121, USA.

Cancer Cell
|September 14, 2021
PubMed

Insights

Palbociclib resistance in breast cancer involves MYC and Cyclin E/CDK2. A new drug, PF-06873600, targets CDK2/4/6 to overcome this resistance, showing promise in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hormone receptor-positive/HER2-negative breast cancer treatment often involves CDK4/6 inhibitors like palbociclib.
  • Resistance to palbociclib limits its long-term efficacy, necessitating the exploration of alternative therapeutic strategies.

Purpose of the Study:

  • To identify mechanisms of palbociclib resistance in breast cancer.
  • To evaluate a novel small molecule inhibitor targeting CDK2, CDK4, and CDK6 to overcome palbociclib resistance.

Main Methods:

  • Preclinical models and clinical transcriptome analysis were used to investigate resistance mechanisms.
  • Pharmacodynamics and in vivo efficacy of PF-06873600 (PF3600) were assessed in multiple tumor models.

Main Results:

  • Palbociclib resistance was linked to the induction of the MYC oncogene and Cyclin E/CDK2 activity.
  • PF-06873600 demonstrated potent inhibition of CDK2/4/6 and efficacy in preclinical models.
  • MYC activity predicted PF3600 efficacy across various cell types.
  • CDK2/4/6 inhibition did not impede anti-tumor immune responses.

Conclusions:

  • Targeting CDK2/4/6 with PF-06873600 offers a potential strategy to overcome palbociclib resistance in breast cancer.
  • PF-06873600 shows therapeutic potential for patients with insufficient response to CDK4/6 inhibitors.
Keywords:
CCNE1CDK2CDK4CDK6MYCcell cyclehormone-receptor-positive breast cancerinnate immune responsepalbociclibtherapy resistance

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