Evidence map›Paper›PMID 41249199›Full record

ArticleNPJ systems biology and applications2025

WEE1 inhibition delays resistance to CDK4/6 inhibitor and antiestrogen treatment in ER+ MCF7 cells.

Wei He, Diane M Demas, Pavel Kraikivski, Ayesha N Shajahan-Haq, William T Baumann

Abstract read
In one paragraph

Article in NPJ systems biology and applications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Wei HeDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Diane M DemasDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Pavel KraikivskiDivision of Systems Biology, Academy of Integrated Science, Virginia Tech, Blacksburg, VA, USA.
Ayesha N Shajahan-HaqDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA. ans33@georgetown.edu.
William T BaumannDepartment of Electrical and Computer Engineering, Virginia Tech, Blacksburg, VA, USA. baumann@vt.edu.

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI MARCUS S NOEL · 1990 to 2026
$71.5M
Optimizing Targeted Breast Cancer Therapy by Mathematical Modeling and Experimental StudiesR01CA201092 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI BAUMANN, WILLIAM THOMAS, SHAJAHAN-HAQ, AYESHA N. · 2016 to 2020
$2.0M
NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA201092U.S. Public Health Service R01-CA201092
6 · The paper itself

Abstract

Although endocrine therapies and Cdk4/6 inhibitors have improved outcomes for patients with estrogen receptor positive (ER+ ) breast cancer, continuous application of these drugs often results in resistance. Upregulation of G1 and S phase kinase activities during therapy can allow cancer cells to bypass drug induced cell cycle arrest. We investigated whether inhibiting WEE1, a key G2 checkpoint regulator also involved in G1/S transition, could delay the development of resistance. We treated ER+ MCF7 breast cancer cells with palbociclib alternating with a combination of fulvestrant and WEE1 inhibitor AZD1775 for 12 months. We found that the alternating treatment delayed the development of drug resistance to palbociclib and fulvestrant compared to monotherapies. We developed a mathematical model that can simulate cell proliferation under monotherapy and alternating drug treatments. Finally, we showed that the mathematical model can be used to minimize the number of fulvestrant plus AZD1775 treatment periods while maintaining its efficacy.

Indexed as

Breast NeoplasmsCell Cycle ProteinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Drug Resistance, NeoplasmEstrogen Receptor ModulatorsNuclear ProteinsProtein-Tyrosine KinasesCell ProliferationFemaleFulvestrantHumansMCF-7 CellsPiperazinesProtein Kinase InhibitorsPyrazolesadavosertibCDK4 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Estrogen Receptor ModulatorsFulvestrantNuclear ProteinspalbociclibPiperazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyridinesPyrimidinonesReceptors, EstrogenWEE1 protein, human

Identifiers

PMID41249199
PMCPMC12624050

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.