Evidence map›Paper›PMID 40565165›Full record

ReviewInternational journal of molecular sciences2025

Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update.

Zhao Zhang, Ritika Harish, Naveed Elahi, Sawanjit Saini, Aamir Telia, Manjit Kundlas, Allexes Koroleva, Israel N Umoh, Manpreet Lota, Meha Bilkhu and 8 more

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
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

18 authors.

Zhao ZhangPennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, 100 East Lancaster Avenue, LIMR R234, Wynnewood, PA 19096, USA.
Ritika HarishPennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, 100 East Lancaster Avenue, LIMR R234, Wynnewood, PA 19096, USA.
Naveed ElahiXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Sawanjit SainiXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Aamir TeliaXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Manjit KundlasXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Allexes KorolevaXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Israel N UmohXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Manpreet LotaXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Meha BilkhuXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Aladdin KawaiahXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Manogna R AllalaXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Armelle LeukeuXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Emmanuel NebuwaXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Nadiya SharifiXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.
Anthony W AshtonXavier University School of Medicine at Aruba, Woodbury, NY 11797, USA.ORCID 0000-0001-6063-1566
Xuanmao JiaoPennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, 100 East Lancaster Avenue, LIMR R234, Wynnewood, PA 19096, USA.
Richard G PestellPennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, 100 East Lancaster Avenue, LIMR R234, Wynnewood, PA 19096, USA.ORCID 0000-0003-3244-8777

Funding

DACH1/Eya Cell fate determination factor and mammary tumorigenesisR01CA132115 · NCI · THOMAS JEFFERSON UNIVERSITY · PI PESTELL, RICHARD G · 2009 to 2018
$3.1M
DOD Breakthrough Breast Cancer Research Program W81XWH-22-BCRPNational Research, Development and Innovation Fund of the Ministry of Culture and Innovation (Hungary) RGH_24 (RGH 151464)NCI NIH HHS R01 CA132115NIH HHS R01CA132115
6 · The paper itself

Abstract

WEE1 kinase is a crucial cell cycle regulatory protein that controls the timing of mitotic entry. WEE1, via inhibition of Cyclin-dependent Kinase 1 (CDK1) and Cyclin-dependent Kinase 2 (CDK2), governs the G2-M checkpoint by inhibiting entry into mitosis. The state of balance between WEE family kinases and CDC25C phosphatases restricts CDK1/CycB activity. The WEE kinase family consists of WEE1, PKMYT1, and WEE2 (WEE1B). WEE1 and PKMYT1 regulate entry into mitosis during cell cycle progression, whereas WEE2 governs cell cycle progression during meiosis. Recent studies have identified WEE1 as a potential therapeutic target in several cancers, including therapy-resistant triple-negative breast cancer. Adavosertib's clinical promise was challenged by inter-individual variations in response and side effects. Because of these promising preclinical outcomes, other WEE1 kinase inhibitors (Azenosertib, SC0191, IMP7068, PD0407824, PD0166285, WEE1-IN-5, Zedoresertib, WEE1-IN-8, and ATRN-1051) are being developed, with several currently being evaluated in clinical trials or as an adjuvant to chemotherapies. Preclinical studies show WEE1 inhibitors induce MHC class 1 antigens and STING when given as combination therapies, suggesting potential additional therapeutic opportunities. Reliable predictors of clinical responses based on mechanistic insights remain an important unmet need. Herein, we review the role of WEE1 inhibition therapy in breast cancer.

Indexed as

Antineoplastic AgentsBreast NeoplasmsCell Cycle ProteinsProtein Kinase InhibitorsProtein-Tyrosine KinasesAnimalsFemaleHumansMolecular Targeted TherapyPyrazolesPyrimidinonesadavosertibAntineoplastic AgentsCell Cycle ProteinsProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinonesWEE1 protein, humanbreast cancercell cycle regulationchemotherapy resistanceclinical trialcyclin-dependent kinasesDNA damage/repairG2/M checkpointmitotic entryWEE1 inhibitorsWEE1 kinase

Identifiers

PMID40565165
PMCPMC12192920

What OpenQuestion holds

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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.