Objective: We aimed to develop novel combinations of inhibitors targeting EGFR family members and c-Met for the treatment of recurrent SCCHN.
Materials And Methods: Three different c-Met inhibitors in combination with a pan-HER inhibitor (crizotinib/afatinib, tivantinib/afatinib and cabozantinib/afatinib) were investigated for their anti-tumor effects on SCCHN cell lines in vitro. In vivo activity of the combinations was tested in SCCHN cell line xenografts and patient-derived xenograft (PDX) animal models generated from patients with recurrent SCCHN.
Results: Western blot assay indicated that activation of EGFR, HER2, HER3, and c-Met was blocked by all three combinations and the downstream PI3K/AKT and ERK signaling pathways were inhibited. Sulforhodamine B colorimetric assay revealed SCCHN cell growth was more effectively inhibited by the combinations than by single agents, particularly in cell lines with high c-Met expression. Furthermore, the combinations were more potent in inducing apoptosis than each of the single agents. In the PDX models, the combination treatments exhibited significantly better efficacy in tumor growth inhibition compared to the respective single agents.
Conclusion: In conclusion, we demonstrated that the simultaneous targeting of EGFR, HER2, and c-Met is more effective than the individual inhibition of these targets in vitro and in SCCHN cell line xenograft and PDX models. Our findings pave the way for further clinical investigation of such combinations in SCCHN.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.oraloncology.2020.105074 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Feasibility and safety of intracranial carotid implantation with covered stents for advanced head and neck squamous cell carcinoma involving the carotid artery: A preliminary investigation.
World J Otorhinolaryngol Head Neck Surg
March 2025
Objective: The aim of this study was to assess the feasibility and safety of implanting covered stents in cases of advanced head and neck squamous cell carcinoma (ASCCHN) where the carotid artery was involved.
Methods: A total of 30 patients (29 males and one female) were included in this study, with ages ranging from 40 to 79 years. Among these patients, 28 patients had received radiotherapy and 17 received subsequent adjuvant therapy, while one was receiving treatment for the first time.
Treatment decision-making factors and sequencing in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Cancer Treat Rev
March 2025
Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Via Rita Levi Montalcini, 4, 20072 Pieve Emanuele, Milan, Italy. Electronic address:
Treatment options for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have evolved over the past decade and have helped improve survival outcomes for patients. Most national and regional guidelines recommend first-line therapy with an immune checkpoint inhibitor (with or without chemotherapy) or a cetuximab-based regimen, by assessment of expression levels of the biomarker programmed cell death-ligand 1 (PD-L1). However, patient- and tumor-specific factors, including the patient's age, comorbidities, performance status, and tumor burden, kinetics and spread also need to be considered to optimize treatment in the first line.
View Article and Find Full Text PDFReal-world Outcomes in Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck With Nivolumab: Galician Study.
Anticancer Res
March 2025
Department of Medical Oncology, Fundación Centro Oncológico de Galicia (COG), A Coruña, Spain.
Background/aim: Real-world evidence regarding the use of nivolumab in metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is limited. This study aimed to describe the clinical characteristics, outcomes, and safety of nivolumab in R/M SCCHN patients treated in routine clinical practice.
Patients And Methods: This retrospective, observational study evaluated the efficacy/safety of nivolumab in 116 patients with R/M SCCHN treated at nine centers within the Galician Group of Head and Neck Cancer health network between 2017 and 2019.
The CD64/CD28/CD3ζ chimeric receptor reprograms T-cell metabolism and promotes T-cell persistence and immune functions while triggering antibody-independent and antibody-dependent cytotoxicity.
Exp Hematol Oncol
February 2025
Department of Biomedicine, Institute of Translational Pharmacology, Italian National Research Council (CNR), Via Fosso del Cavaliere 100, Rome, 00133, Italy.
Background: Recent studies have shown that CD32/CD8a/CD28/CD3ζ chimeric receptor cells directly kill breast cancer cells, suggesting the existence of cell surface myeloid FcγR alternative ligands (ALs). Here, we investigated the metabolism, ALs, cytotoxicity, and immunoregulatory functions of CD64/CD28/CD3ζ in colorectal cancer (CRC) and squamous cell carcinoma of the head and neck.
Methods: The CD64/CD28/CD3ζ -SFG retroviral vector was used to produce viruses for T-cell transduction.
To Determine the Role of Human Papillomavirus in Oral Cancer-A Prospective Study.
J Pharm Bioallied Sci
December 2024
Department of Public Health Dentistry, Teerthanker Mahaveer Dental College and Research Centre, Moradabad, Uttar Pradesh, India.
Introduction: Human papillomavirus (HPV) has been implicated in several studies pertaining to oral squamous cell carcinoma (OSCC) in the last several decades. Infection with human papillomavirus (HPV), particularly HPV16 and 18, is the leading cause of squamous cell carcinoma of the neck (SCCHN).
Methodology: We selected an adequate number of subjects with the same parameters for both the case and the controls based on detailed case histories, specifically taking into account the adverse habits (tobacco in any form and alcohol) that each subject had recorded.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!