Evidence map›Paper›PMID 41339342›Full record

ArticleNPJ breast cancer2025

CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen.

Nealia C House, Maxine M Chen, Sima Khazaei, Victoria Brown, Philip Ramsden, David H Peng, Sydney Moore, Liang Yuan, Rentian Wu, Fangyang Wang and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ breast cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Nealia C House *Blueprint Medicines Corporation, Cambridge, MA, USA. NHouse@blueprintmedicines.com.
Maxine M Chen *Blueprint Medicines Corporation, Cambridge, MA, USA.
Sima KhazaeiTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Victoria BrownBlueprint Medicines Corporation, Cambridge, MA, USA.
Philip RamsdenBlueprint Medicines Corporation, Cambridge, MA, USA.
David H PengTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sydney MooreBlueprint Medicines Corporation, Cambridge, MA, USA.
Liang YuanBlueprint Medicines Corporation, Cambridge, MA, USA.
Rentian WuBlueprint Medicines Corporation, Cambridge, MA, USA.
Fangyang WangTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Linjie LuoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ningping FengTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Christopher A BristowTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Timothy A YapDepartment of Investigational Cancer Therapeutics, Therapeutic Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Khandan KeyomarsiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph R MarszalekTRACTION - Translational Research to AdvanCe Therapeutics and Innovation in ONcology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Scott RibichBlueprint Medicines Corporation, Cambridge, MA, USA.
Mikael L RinneBlueprint Medicines Corporation, Cambridge, MA, USA.
Lakshmi B MuthuswamyBlueprint Medicines Corporation, Cambridge, MA, USA.
Kerrie L FaiaBlueprint Medicines Corporation, Cambridge, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant cyclin-dependent kinase 2 (CDK2) activity is implicated as a resistance mechanism to CDK4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Using preclinical patient-derived xenograft models, the CDK2i + CDK4/6i combination was active broadly across CDK4/6i-resistant and -naïve HR+ and triple-negative breast cancer models. A novel, weighted mRNA expression signature involving CCND1, CCNE1, RB1, and CDKN2A (p16) predicted response to combined inhibition of CDK2 and CDK4/6. Addition of endocrine therapy significantly enhanced antitumor activity in HR+ models, providing preclinical proof-of-concept for the broad antitumor activity of the triple combination. Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.

Identifiers

PMID41339342
PMCPMC12675586

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.