ArticleCancer research2025
Profiling the Activity of the Potent and Highly Selective CDK2 Inhibitor BLU-222 Reveals Determinants of Response in CCNE1-Aberrant Ovarian and Endometrial Tumors.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.The Biochemical journal · 2026Article
- Transcriptional Heterogeneity in Dedifferentiated Liposarcoma Reveals Distinct Cell-Cycle Subtypes.Annals of surgical oncology · 2026Article
- Castration-resistant prostate cancer cells are addicted to the high activity of cyclin-dependent kinase 2.Molecular oncology · 2026Article
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Precision targeting ofTranslational cancer research · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- Article
- CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen.NPJ breast cancer · 2025Article
- Multiomic analysis of CCNE1 amplification associated molecular and immune features in gynecological cancers.Discover oncology · 2025Article
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
- p16 expression confers sensitivity to CDK2 inhibitors in cyclin E1-driven ovarian cancers.Science signaling · 2025Article
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222.Cancer research · 2025Article
- Genomic instability andFrontiers in oncology · 2025Article
- Cell Cycle Plasticity and Heterogeneity: An Underappreciated Feature of Cancer and Treatment Response.Cancer heterogeneity and plasticity · 2025Article
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11 authors.
Funding
Abstract
BLU-222 is an investigational, potent, highly selective, orally bioavailable cyclin-dependent kinase 2 (CDK2) inhibitor in clinical development. BLU-222 demonstrated robust antitumor activity in select CCNE1-high ovarian and endometrial cancer models. We used a combination of CRISPR whole-genome screens coupled with targeted genetic and pharmacologic approaches in ovarian and endometrial cell lines to identify biological determinants to predict BLU-222 monotherapy activity. Rb and p16 expression were biomarkers that enriched for CDK2-dependency/BLU-222 sensitivity in CCNE1-overexpressed, nonamplified cells. Furthermore, intact Rb and low p16 expression predicted a BLU-222 and CDK4/6 inhibitor combination response. BLU-222 demonstrated robust activity in combination with carboplatin or paclitaxel in CCNE1-aberrant models, rendering chemotherapy-resistant tumors strongly sensitive to the combination. These findings demonstrate that response to CDK2 inhibition by BLU-222 can be further predicted using a combinatorial biomarker signature that could refine patient selection criteria in CCNE1-high patients and support clinical development. Significance: The identification of biomarkers of response to the CDK2-selective inhibitor BLU-222 and effective combinations with CDK4/6 inhibitors or chemotherapy could enable precision medicine strategies for CDK2 inhibition in ovarian and endometrial cancer. See related article by Dommer and colleagues, p. 1310.
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