ArticleCell reports. Medicine2024
Targeting WEE1 enhances the antitumor effect of KRAS-mutated non-small cell lung cancer harboring TP53 mutations.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed.
- Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review).Oncology reports · 2026Review
- Genetic insights into lung squamous cell carcinoma: howTranslational cancer research · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Article
- ResMap: A community resource for systematic mapping of therapy-persistent residual cancer cell dependencies across contexts.Science advances · 2026Article
- AZD6738 overcomes acquired olaparib resistance in BRCA1 mutation triple-negative breast cancer through down-regulation of BRCA2 and RAD51.Scientific reports · 2026Article
- Systematic and precise interventions for KRAS-mutant cancers.Experimental hematology & oncology · 2026Review
- Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C Inhibitors.Cancer research · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Context-aware gene dependency modeling via graph attention networks for precision oncology.Journal of translational medicine · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Targeting WEE1 to Overcome ARID1A Mutation-Driven Osimertinib Resistance in EGFR-Mutant Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Article
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
- Azenosertib Is a Potent and Selective WEE1 Kinase Inhibitor with Broad Antitumor Activity Across a Range of Solid Tumors.Molecular cancer therapeutics · 2025Article
- Differential Response and Resistance to KRAS-Targeted Therapy.Molecular carcinogenesis · 2025Review
- Brazilin Inhibits the Proliferation of Non-Small Cell Lung Cancer by Regulating the STING/TBK1/IRF3 Pathway.Journal of cellular and molecular medicine · 2025Article
- The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Activity with KRASG12C Inhibitors in Preclinical Models.Cancer research communications · 2025Article
- Therapeutic strategies for KRAS G12C-mutant non-small cell lung cancer: from bench to bedside and beyond.Frontiers in pharmacology · 2025Review
- Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical development of Kirsten rat sarcoma virus (KRAS)-G12C inhibitors for the treatment of KRAS-mutant lung cancer is limited by the presence of co-mutations, intrinsic resistance, and the emergence of acquired resistance. Therefore, innovative strategies for enhancing apoptosis in KRAS-mutated non-small cell lung cancer (NSCLC) are urgently needed. Through CRISPR-Cas9 knockout screening using a library of 746 crRNAs and drug screening with a custom library of 432 compounds, we discover that WEE1 kinase inhibitors are potent enhancers of apoptosis, particularly in KRAS-mutant NSCLC cells harboring TP53 mutations. Mechanistically, WEE1 inhibition promotes G2/M transition and reduces checkpoint kinase 2 (CHK2) and Rad51 expression in the DNA damage response (DDR) pathway, which is associated with apoptosis and the repair of DNA double-strand breaks, leading to mitotic catastrophe. Notably, the combined inhibition of KRAS-G12C and WEE1 consistently suppresses tumor growth. Our results suggest targeting WEE1 as a promising therapeutic strategy for KRAS-mutated NSCLC with TP53 mutations.
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Registered trials
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.