ArticleCancer research2018
Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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, 41 citations in OpenAlex.
- Article
- Review
- Clinical and genomic characterization of chemoradiation-resistant HPV-positive oropharyngeal squamous cell carcinoma.Frontiers in oncology · 2024Article
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Biomarkers and 3D models predicting response to immune checkpoint blockade in head and neck cancer (Review).International journal of oncology · 2022Review
- Diagnostics of HNSCC Patients: An Analysis of Cell Lines and Patient-Derived Xenograft Models for Personalized Therapeutical Medicine.Diagnostics (Basel, Switzerland) · 2022Review
- Article
- IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer.Cancers · 2021Article
- Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.Nature communications · 2021Article
- Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review.Frontiers in oncology · 2021Review
- MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.PLoS pathogens · 2021Article
- Gastric Cancer Harboring anOncoTargets and therapy · 2021Article
- Phytochemicals as Potential Chemopreventive and Chemotherapeutic Agents for Emerging Human Papillomavirus-Driven Head and Neck Cancer: Current Evidence and Future Prospects.Frontiers in pharmacology · 2021Review
- CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2020Article
- Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns.Frontiers in cellular and infection microbiology · 2020Review
- Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma.Frontiers in oncology · 2020Review
- Review
- Review
- Review
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.
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What OpenQuestion 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 OpenQuestion graph.