ArticleProceedings of the National Academy of Sciences of the United States of America2020
FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Therapeutic scheduling of WEE1 inhibition preserves T cell function and promotes immune control of HPVbioRxiv : the preprint server for biology · 2026Article
- Therapeutic resistance in HPV-positive oropharyngeal squamous cell carcinoma: molecular mechanisms, clinical challenges, and precision strategies.Frontiers in genetics · 2026Review
- Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer.Journal of the National Cancer Institute · 2025Article
- A proteogenomic analysis of cervical cancer reveals therapeutic and biological insights.Nature communications · 2024Article
- Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.bioRxiv : the preprint server for biology · 2024Article
- Functional RNAi Screening Identifies G2/M and Kinetochore Components as Modulators of TNFα/NF-κB Prosurvival Signaling in Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2024Article
- Article
- Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma.Cancers · 2023Article
- Myt1 overexpression mediates resistance to cell cycle and DNA damage checkpoint kinase inhibitors.Frontiers in cell and developmental biology · 2023Article
- GA-OH enhances the cytotoxicity of photon and proton radiation in HPVFrontiers in oncology · 2023Article
- The Drivers, Mechanisms, and Consequences of Genome Instability in HPV-Driven Cancers.Cancers · 2022Review
- Inhibiting WEE1 and IKK-RELA Crosstalk Overcomes TNFα Resistance in Head and Neck Cancers.Molecular cancer research : MCR · 2022Article
- Article
- TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation.NAR cancer · 2022Article
- Article
- WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway.The Journal of experimental medicine · 2022Article
- Targeting DNA damage response as a potential therapeutic strategy for head and neck squamous cell carcinoma.Frontiers in oncology · 2022Review
- Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1.Frontiers in oncology · 2022Review
- FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer.Cancers · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) associated with high-risk human papilloma virus (HPV) infection is a growing clinical problem. The WEE1 kinase inhibitor AZD1775 (WEE1i) overrides cell cycle checkpoints and is being studied in HNSCC regimens. We show that the HPV16 E6/E7 oncoproteins sensitize HNSCC cells to single-agent WEE1i treatment through activation of a FOXM1-CDK1 circuit that drives mitotic gene expression and DNA damage. An isogenic cell system indicated that E6 largely accounts for these phenotypes in ways that extend beyond p53 inactivation. A targeted genomic analysis implicated FOXM1 signaling downstream of E6/E7 expression and analyses of primary tumors and The Cancer Genome Atlas (TCGA) data revealed an activated FOXM1-directed promitotic transcriptional signature in HPV+ versus HPV- HNSCCs. Finally, we demonstrate the causality of FOXM1 in driving WEE1i sensitivity. These data suggest that elevated basal FOXM1 activity predisposes HPV+ HNSCC to WEE1i-induced toxicity and provide mechanistic insights into WEE1i and HPV+ HNSCC therapies.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.