Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low‐risk patient as defined by targeted sequencing

Tillman, Brittny N.; Yanik, Megan; Birkeland, Andrew C.; Liu, Chia Jen; Hovelson, Daniel H.; Cani, Andi K.; Palanisamy, Nallasivam; Carskadon, Shannon; Carey, Thomas E.; Bradford, Carol R.; Tomlins, Scott A.; McHugh, Jonathan B.; Spector, Matthew E.; Brenner, J. Chad

doi:10.1002/hed.24292

Cited by 33 publications

(30 citation statements)

References 33 publications

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“…(15,16) In HNSCC, genetic alterations of not only EGFR but also ERBB2, FGFR1, FGFR3, and MET have been reported. (17)(18)(19)(20)(21) RTK gene alterations induce epithelial-mesenchymal transition, (22) allowing tumor cells to acquire migration capabilities. Overexpression of EGFR was demonstrated to be an adverse prognostic factor in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

et al. 2017

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This study aimed to clarify the genomic factors associated with the diagnosis and prognosis of oral squamous cell carcinoma via next‐generation sequencing. We evaluated data from 220 cases of oral squamous cell carcinoma. Genomic DNA was eluted using formalin‐fixed, paraffin‐embedded samples, and targeted resequencing of 50 cancer‐related genes was performed. In total, 311 somatic mutations were detected in 220 patients, consisting of 68 synonymous mutations and 243 non‐synonymous mutations. Genes carrying mutations included TP53, CDKN2A, and PIK3CA in 79 (35.9%), 35 (15.9%), and 19 patients (8.6%), respectively. Copy number analysis detected amplification of PIK3CA and AKT1 in 38 (17.3%) and 11 patients (5.0%), respectively. Amplification of receptor tyrosine kinases was found in 37 patients (16.8%). Distant metastasis was noted in nine of 37 patients (24%) with receptor tyrosine kinase amplification, accounting for 43% of the 21 cases of distant metastasis. The cumulative 5‐year survival rate was 64.6% in the receptor tyrosine kinase amplification group vs 85.2% in the no receptor tyrosine kinase amplification group. Moreover, we identified significantly poorer prognosis in the TP53 mutation/receptor tyrosine kinase amplification group, for which the cumulative 5‐year survival rate was 41.6%. In conclusion, the results of this study demonstrated that receptor tyrosine kinase amplification is a prognostic factor for distant metastasis of oral squamous cell carcinoma, indicating the necessity of using next‐generation sequencing in clinical sequencing.

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Section: Discussionmentioning

confidence: 99%

Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

et al. 2017

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“…Indeed, our analysis found a potential driver amplification of the tyrosine kinase receptor FGFR1 . Extending the discovery to The Cancer Genome Atlas (TCGA) HNSCC cohort, we demonstrated that the FGF/FGFR pathway is dysregulated in >30% of HNSCCs and likely represents a previously unrecognized aberration driving disease pathogenesis [ 10 ]. Consequently, carefully designed studies focusing on the genetics of under-studied epidemiologic populations can be very informative.…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

et al. 2016

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While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

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“…no. 111-035-045; Jackson ImmunoResearch, West Grove, PA) secondary antibody at room temperature for 1 hour as described elsewhere (Tillman et al, 2016). The blots were then visualized with chemiluminescence and imaged.…”

Section: Methodsmentioning

confidence: 99%

Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma

et al. 2019

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Head and neck squamous cell carcinoma (HNSCC) is a common and debilitating form of cancer characterized by poor patient outcomes and low survival rates. In HNSCC, genetic aberrations in phosphatidylinositol 3-kinase (PI3K) and epidermal growth factor receptor (EGFR) pathway genes are common, and small molecules targeting these pathways have shown modest effects as monotherapies in patients. Whereas emerging preclinical data support the combined use of PI3K and EGFR inhibitors in HNSCC, inhuman studies have displayed limited clinical success so far. Here, we examined the responses of a large panel of patient-derived HNSCC cell lines to various combinations of PI3K and EGFR inhibitors, including EGFR agents with varying specificity and mechanistic characteristics. We confirmed the efficacy of PI3K and EGFR combination therapies, observing synergy with a isoform-selective PI3K inhibitor HS-173 and irreversible EGFR/ERBB2 dual inhibitor afatinib in most models tested. Surprisingly, however, our results demonstrated only modest improvement in response to HS-173 with reversible EGFR inhibitor gefitinib. This difference in efficacy was not explained by differences in ERBB target selectivity between afatinib and gefitinib; despite effectively disrupting ERBB2 phosphorylation, the addition of ERBB2 inhibitor CP-724714 failed to enhance the effect of HS-173 gefitinib dual therapy. Accordingly, although irreversible ERBB inhibitors showed strong synergistic activity with HS-173 in our models, none of the reversible ERBB inhibitors were synergistic in our study. Therefore, our results suggest that the ERBB inhibitor mechanism of action may be critical for enhanced synergy with PI3K inhibitors in HNSCC patients and motivate further preclinical studies for ERBB and PI3K combination therapies.

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Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low‐risk patient as defined by targeted sequencing

Cited by 33 publications

References 33 publications

Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma

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