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Article

WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASG12C-mutant lung cancer.

Cell death & disease - 30 Aug 2025

Zhou Chao, Liu Yuqing, Liu Hongyu, Lu Jun, Zhang Bo, Zhu Liang, Wang Shuyuan, Lei Huimin, Han Baohui

Abstract excerpt

The clinical effect of KRAS G12C inhibitors (G12Ci) as monotherapy is poor, prompting the development of combination treatment strategies. Here, we demonstrate that the WEE1 kinase inhibitor (WEE1i), Adavosertib, can sensitize the effect of G12Ci through the MYBL2-RRM2 axis, which is associated with poor prognosis in lung cancer. Overexpressing the MYBL2-RRM2 axis or supplementing the products of the RRM2 enzyme,...

Read the complete abstract on PubMed

Topics

Humans
Lung Neoplasms
Animals
Proto-Oncogene Proteins p21(ras)
Protein-Tyrosine Kinases
Mice

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Protein Kinase Inhibitors

Drug Synergism

Cell Line, Tumor

Cell Cycle Proteins

Xenograft Model Antitumor Assays

Pyrazoles

Mice, Nude

Mutation

Ribonucleoside Diphosphate Reductase

Female

Pyrimidines

Pyrimidinones

Source

Open in PubMed Open full text

Identifiers

PMID: 40885709
DOI: 10.1038/s41419-025-07992-4
PMCID: PMC12398517

Genes

MYBL2
WEE1
KRAS

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 21 Oct 2026.

Related research

Semantic proximity does not establish scientific evidence. Graph snapshot: 2026-09-29.

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WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASG12C-mutant lung cancer.PMID 40885709Read ↗

WEE1 confers resistance to KRASG12C inhibitors in non-small cell lung cancer.Semantic proximity Read ↗

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Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance.Semantic proximity Read ↗

Inhibition of ULK1/2 and KRAS <sup>G12C</sup> controls tumor growth in preclinical models of lung cancerSemantic proximity Read ↗

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Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.Semantic proximity Read ↗

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The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer.Semantic proximity Read ↗

Romidepsin inhibits NRF2 and enhances the efficacy of adagrasib by inducing autophagic cell death in KRAS-mutant tumor cells.Semantic proximity Read ↗

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