Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumor and vascular endothelial cells

Dellacono, Frank R.; Spiro, Jeffrey D.; Eisma, Roselle J.; Kreutzer, Donald L.

doi:10.1016/s0002-9610(97)00169-4

Cited by 62 publications

(55 citation statements)

References 13 publications

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“…Our finding that 82% of HPV-positive and 75% of HPVnegative HNSCC overexpress FGFR1 is in concordance with previous reports, but it differs from a study by Freier and colleagues, which reported high FGFR1 expression in only 12% of OSCC (5,17,31,32). In addition, we observed prognostic value for FGFR1 protein expression in HPV-negative HNSCC, which has not been reported by previous studies, although Hase and colleagues reported prognostic value for FGFR1 expression in oral cancer-associated fibroblast (32,33).…”

Section: Discussionsupporting

confidence: 86%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.Results: FGFR1 protein overexpression occurred in 82% (36/ 44) of human papillomavirus (HPV)-positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74-6.90; P ¼ 0.001 and HR, 1.53; 95% CI, 1.04-2.39; P ¼ 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor-resistant HNSCC patients. Clin Cancer Res; 22(15); 3884-93. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 86%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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“…For example, high expression levels of FGF2, a well-characterized angiogenic factor, but also FGF1, FGFR1 and FGFR2, have been linked to the progression of HNSCC. [22][23][24] However, a role for FGFR4 in this type of tumor has not yet been determined.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma

Streit

Bange²,

Fichtner

et al. 2004

Intl Journal of Cancer

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After decades of rigorous investigations of chemotherapeutic cancer therapies, many cancers, including those of the head and neck, remain beyond our clinical ability to control them. From 3% to 5% of all patients initially cured of early-stage head and neck cancer will develop second primary tumors or local recurrences. 1 This phenomenon has been explained by the concept of field cancerization, which argues that certain risk factors such as alcohol and tobacco change the lining of the upper aerodigestive tract into a so-called condemned mucosa. In such a scenario, alcohol may represent the key risk factor for neoplastic transformation in the oral cavity, the oro-and hypopharynx. [2][3][4] An increasing amount of evidence suggests that alcohol intake and smoking play a synergistic role in the neoplastic progress.One of the most important achievements of molecular oncology has been the demonstration that cancer represents a genetic disease that begins with genetic damages in the genome of one cell in the form of point mutations, DNA rearrangement and gene amplification leading to the distortion of the expression and biochemical function of respective gene products. Growth factor receptors of the class I subfamily, which include the epidermal growth factor receptor (EGFR/HER1) and the related proteins HER2, HER3 and HER4, have shown that amplification or overexpression of those receptors, especially well documented for HER2 in patients with breast and ovarian cancers, plays an important role in carcinogenesis and tumor progression. [5][6][7][8] Multivariate survival analysis showed that HER2 amplification or overexpression is more predictive of clinical outcome than all other known prognosticators with the exception of positive lymph nodes. 9,10 These findings have validated the HER2 receptor as a target for therapeutic intervention. Moreover, recent clinical investigations have confirmed the benefit of antagonistic HER2 antibody therapy in breast cancer using herceptin. 11 Minute genetic changes such as point mutations have been found to cause constitutive activation of the HER2/neu kinase activity and to induce neoplastic disorders. 12 Similarly, the 2 amino acid substitutions Gly380Arg and Ala391Glu in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) have been shown to be responsible for 2 forms of human dwarfism, namely, achondroplasia and morbus crouzon. [13][14][15] Other mutations in the FGFR3 gene have been associated with bladder and cervix cancer. 16 The FGFR signaling system is composed of 4 receptor tyrosine kinases (RTKs) and more than 20 known ligands and has been implicated in the regulation of a multitude of both physiologic and pathophysiologic processes, including migration, wound healing, angiogenesis and cancer. 17 More recently, we have identified a single nucleotide polymorphism (SNP) in codon 388 of the FGFR4 gene, which plays a pivotal role in the progression of breast cancer. This SNP is present at a significantly higher rate in breast cancer patients with early relap...

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“…Abnormal expression of FGFs in the environment surrounding malignant cells has been reported in head and neck squamous carcinoma (134). Moreover, studies from a mouse model, which allows for genetic manipulation of the prostate epithelium and mesenchyme, independently showed that enhanced expression of mesenchymal FGF10 was sufficient to induce epithelial transformation and the formation of well-differentiated prostate carcinoma (135).…”

Section: Availability Of Ligandmentioning

confidence: 99%

Roles of Fibroblast Growth Factor Receptors in Carcinogenesis

Haugsten

Wiedlocha

Olsnes

et al. 2010

Molecular Cancer Research

274

226

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The fibroblast growth factor receptors (FGFR) play essential roles both during development and in the adult. Upon ligand binding, FGFRs induce intracellular signaling networks that tightly regulate key biological processes, such as cell proliferation, survival, migration, and differentiation. Deregulation of FGFR signaling can thus alter tissue homeostasis and has been associated with several developmental syndromes as well as with many types of cancer. In human cancer, FGFRs have been found to be deregulated by multiple mechanisms, including aberrant expression, mutations, chromosomal rearrangements, and amplifications. In this review, we will give an overview of the main FGFR alterations described in human cancer to date and discuss their contribution to cancer progression.

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Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumor and vascular endothelial cells

Cited by 62 publications

References 13 publications

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma

Roles of Fibroblast Growth Factor Receptors in Carcinogenesis

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