ArticleOral oncology2016
Co-targeting ALK and EGFR parallel signaling in oral squamous cell carcinoma.
Article in Oral oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Advancements and Clinical Applications Prospects of Epigenetic Biomarkers in Liquid Biopsy for Oral Squamous Cell Carcinoma.Current issues in molecular biology · 2026Review
- Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma.Molecular carcinogenesis · 2025Article
- Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).Oncology reports · 2024Review
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer.Cancers · 2022Article
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
- Prognostic value of theArchives of medical science : AMS · 2021Article
- The novel capsazepine analog, CIDD-99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1-independent induction of ER stress, mitochondrial dysfunction, and apoptosis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2019Article
- Novel polygodial analogs P3 and P27: Efficacious therapeutic agents disrupting mitochondrial function in oral squamous cell carcinoma.International journal of oncology · 2018Article
- Thymol inhibits oral squamous cell carcinoma growth via mitochondria-mediated apoptosis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2018Article
- CD109 and squamous cell carcinoma.Journal of translational medicine · 2018Review
- DKK3 Overexpression Increases the Malignant Properties of Head and Neck Squamous Cell Carcinoma Cells.Oncology research · 2018Article
- Induction of anaplastic lymphoma kinase (ALK) as a novel mechanism of EGFR inhibitor resistance in head and neck squamous cell carcinoma patient-derived models.Cancer biology & therapy · 2018Article
- EGFR and Cortactin: Markers for potential double target therapy in oral squamous cell carcinoma.Experimental and therapeutic medicine · 2017Article
- ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity.In vivo (Athens, Greece)Article
- Combined EGFR/ALK Expression Analysis in Laryngeal Squamous Cell Carcinoma.In vivo (Athens, Greece)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Squamous cell carcinoma (SCC) comprises 90% of all head and neck cancers and has a poor survival rate due to late-stage disease that is refractive to traditional therapies. Epidermal growth factor receptor (EGFR) is over-expressed in greater than 80% of head and neck SCC (HNSCC). However, EGFR targeted therapies yielded little to no efficacy in clinical trials. This study investigated the efficacy of co-targeting EGFR and the anaplastic lymphoma kinase (ALK) whose promoter is hypomethylated in late-stage oral SCC (OSCC). We observed increased ALK activity in late-stage human OSCC tumors and invasive OSCC cell lines. We also found that while ALK inhibition alone had little effect on proliferation, co-targeting ALK and EGFR significantly reduced OSCC cell proliferation in vitro. Further analysis showed significant efficacy of combined treatment in HSC3-derived xenografts resulting in a 30% decrease in tumor volumes by 14days (p<0.001). Western blot analysis showed that co-targeting ALK and EGFR significantly reduced EGFR phosphorylation (Y1148) in HSC3 cells but not Cal27 cells. ALK and EGFR downstream signaling interactions are also demonstrated by Western blot analysis in which lone EGFR and ALK inhibitors attenuated AKT activity whereas co-targeting ALK and EGFR completely abolished AKT activation. No effects were observed on ERK1/2 activation. STAT3 activity was significantly induced by lone ALK inhibition in HSC3 cells and to a lower extent in Cal27 cells. Together, these data illustrate that ALK inhibitors enhance anti-tumor activity of EGFR inhibitors in susceptible tumors that display increased ALK expression, most likely through abolition of AKT activation.
Indexed as
Identifiers
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.