We examined the relationship of EGFR ligands, EGF, transforming growth factor-alpha,and amphiregulin and the efficacy of gefitinib and cetuximab in EGFR wild-type NSCLC (n=10) and head and neck squamous cell carcinoma (n=4) cell lines.
To identify genes that are specifically methylated during the evolution of resistance to anti-EGFR therapeutic agents, we performed a methylation-specific array containing a panel of 56 genes that are commonly known to be regulated through promoter methylation in two parental non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cell lines and their resistant derivatives to either erlotinib or cetuximab.
In this study, we found that the addition of CHKi to the EGFR inhibitor cetuximab with and without radiotherapy significantly decreased cell proliferation and survival fraction in human papillomavirus virus (HPV)-positive and HPV-negative HNSCC cell lines.
Head and neck squamous cell carcinoma is frequently associated with aberrant epidermal growth factor receptor (EGFR) signaling, which contributes to tumor growth.
Targeted therapy against the epidermal growth factor receptor (EGFR) only variably represents a therapeutic advance in head and neck squamous cell carcinoma (HNSCC).
The tumor antigen (TA)-targeted monoclonal antibodies (mAb) cetuximab and panitumumab target the human epidermal growth factor receptor and have been integrated into treatment regimens for advanced squamous cell carcinoma of the head and neck (SCCHN).
After establishment of the protocol by using spiking experiments, its suitability to determine the absolute number of CTCs as well as their expression of epidermal growth factor receptor (EGFR) and its phosphorylated form (phospho-EGFR) in blood samples from patients with squamous cell carcinoma of the head and neck (SCCHN) was validated.
These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens.
Our study revealed high frequency of EGFR overexpression (66-84%), low frequency of gene amplification (10-32.5%) and absence of functional mutation in the dysplastic lesions and HNSCC samples.
We have previously demonstrated that RA down-modulates transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) levels in head and neck squamous cell carcinoma by decreasing the transcription rate of these two genes.
Resistance to epidermal growth factor receptor (EGFR)-targeted therapy is insufficiently understood in head and neck squamous cell carcinoma (HNSCC), entailing the lack of predictive biomarkers.Here, we studied resistance-mediating EGFR ectodomain and activating RAS mutations by next-generation sequencing (NGS) of cell lines and tumor tissue of cetuximab-naïve patients (46 cases, 12 cell lines), as well as liquid biopsies taken during and after cetuximab/platinum/5-fluorouracil treatment (20 cases).
These experiments indicate that EGFR gene expression and function is critical for SCCHN cell growth but not for growth of normal mucosa cells and therefore may serve as a tumor-specific target for preventive and therapeutic strategies in head and neck cancer.
We previously demonstrated that biopsy specimens and established cell lines from patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress TGF-alpha and its receptor, epidermal growth factor receptor (EGFR) at both the mRNA and protein levels.
Although modern surgery, radiation, and conventional chemotherapy strategies for HNSCC continue to provide gradual improvement in outcome, the first molecular targeting approach to show a survival advantage for HNSCC patients has recently emerged in the context of epidermal growth factor receptor biology.
Overall, our results highlight EGFR-K<sub>521</sub> expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients.
The EGFR-targeted antibody cetuximab is effective against head and neck cancer (HNSCC), but in only 15% to 20% of patients, and the variability and extent of cetuximab-mediated cellular immunity is not fully understood.
Importantly, recent evidence has emerged supporting also an immune-modulatory effect of EGFR inhibition, and interest has now focused on utilizing these effects in the current treatment approaches for SCCHN.
Interestingly, we show that EGFR blockade inhibits <i>EREG</i> expression, and that <i>EREG</i> knock-down decreases basal cell clonogenic survival, suggesting that <i>EREG</i> expression could be a predictive functional marker of sensitivity to EGFR blockade in basal-like HNSCC.
In conclusion, our results show that the combination of CD44 (high) and EGFR (low) cell surface expression can be used to identify a treatment resistant subpopulation with an EMT phenotype in HNSCC cell lines.