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Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update

Zhao Zhang1, Ritika Harish1, Naveed Elahi2

  • 1Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, 100 East Lancaster Avenue, LIMR R234, Wynnewood, PA 19096, USA.

International Journal of Molecular Sciences
|June 26, 2025
PubMed

Insights

WEE1 kinase inhibitors show promise for treating breast cancer, especially triple-negative types. New drugs are in development, with potential for combination therapies and improved patient response prediction.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • WEE1 kinase is a key regulator of the G2-M checkpoint, controlling entry into mitosis by inhibiting CDK1/CDK2.
  • The WEE kinase family includes WEE1, PKMYT1, and WEE2, with WEE1 and PKMYT1 involved in mitotic entry and WEE2 in meiosis.
  • WEE1 is a promising therapeutic target in various cancers, including therapy-resistant triple-negative breast cancer.

Purpose of the Study:

  • To review the role of WEE1 inhibition therapy in breast cancer treatment.
  • To discuss the development and clinical evaluation of novel WEE1 kinase inhibitors.
  • To explore potential combination therapies and the need for response predictors.

Main Methods:

  • Literature review of WEE1 kinase function, inhibition, and therapeutic applications in breast cancer.
  • Analysis of preclinical and clinical data for WEE1 inhibitors.
  • Examination of mechanisms of action, including immune modulation.

Main Results:

  • WEE1 inhibition is being explored as a therapeutic strategy for breast cancer, with several inhibitors in clinical trials.
  • Adavosertib showed clinical promise but faced challenges with response variability and side effects.
  • Preclinical studies suggest WEE1 inhibitors can enhance anti-cancer immunity through MHC class I and STING induction.

Conclusions:

  • WEE1 kinase inhibitors represent a developing therapeutic avenue for breast cancer.
  • Further research is needed to identify reliable predictors of clinical response to WEE1 inhibition.
  • Combination therapies involving WEE1 inhibitors may offer enhanced efficacy and novel therapeutic opportunities.
Keywords:
DNA damage/repairG2/M checkpointWEE1 inhibitorsWEE1 kinasebreast cancercell cycle regulationchemotherapy resistanceclinical trialcyclin-dependent kinasesmitotic entry

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