ArticleThe Journal of clinical investigation2023
ODF2L acts as a synthetic lethal partner with WEE1 inhibition in epithelial ovarian cancer models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Pooled it
- PKMYT1 in Cancer: Beyond Cell Cycle Checkpoints to Context-Dependent Therapeutic Vulnerability.Genes, chromosomes & cancer · 2026Review
- SHAP-interpretable machine learning integrating exposures and multi-omics reveals immune alterations and biomarkers in COPD-lung cancer comorbidity.Frontiers in immunology · 2026Article
- METAP2 inhibits K48-linked ubiquitination of YTHDF2 to promote ovarian cancer progression.Oncogene · 2025Article
- Lactate Enhances Non-Homologous End Joining Repair and Chemoresistance Through Facilitating XRCC4-LIG4 Complex Assembly in Ovarian Cancer.Biomedicines · 2025Article
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
- A noncanonical role of SAT1 enables anchorage independence and peritoneal metastasis in ovarian cancer.Nature communications · 2025Article
- ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Predictive value of preoperative systemic immune-inflammation index and prognostic nutrition index in patients with epithelial ovarian cancer.Journal of ovarian research · 2025Review
- Plectin, a novel regulator in migration, invasion and adhesion of ovarian cancer.Cell & bioscience · 2025Article
- Exploring the molecular interface of gene expression dynamics and prostate cancer susceptibility in response to HBCD exposure.Toxicology research · 2025Article
- Article
- Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.Nature communications · 2024Article
- Targeting WEE1 Kinase in Gynecological Malignancies.Drug design, development and therapy · 2024Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
WEE1 has emerged as an attractive target in epithelial ovarian cancer (EOC), but how EOC cells may alter their sensitivity to WEE1 inhibition remains unclear. Here, through a cell cycle machinery-related gene RNAi screen, we found that targeting outer dense fiber of sperm tails 2-like (ODF2L) was a synthetic lethal partner with WEE1 kinase inhibition in EOC cells. Knockdown of ODF2L robustly sensitized cells to treatment with the WEE1 inhibitor AZD1775 in EOC cell lines in vitro as well as in xenografts in vivo. Mechanistically, the increased sensitivity to WEE1 inhibition upon ODF2L loss was accompanied by accumulated DNA damage. ODF2L licensed the recruitment of PKMYT1, a functionally redundant kinase of WEE1, to the CDK1-cyclin B complex and thus restricted the activity of CDK1 when WEE1 was inhibited. Clinically, upregulation of ODF2L correlated with CDK1 activity, DNA damage levels, and sensitivity to WEE1 inhibition in patient-derived EOC cells. Moreover, ODF2L levels predicted the response to WEE1 inhibition in an EOC patient-derived xenograft model. Combination treatment with tumor-targeted lipid nanoparticles that packaged ODF2L siRNA and AZD1775 led to the synergistic attenuation of tumor growth in the ID8 ovarian cancer syngeneic mouse model. These data suggest that WEE1 inhibition is a promising precision therapeutic strategy for EOC cells expressing low levels of ODF2L.
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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.