Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review

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Abstract

Background

Since head and neck cancer is characterized by poor survival rates, there is a demand for novel therapeutic targets and prognostic biomarkers. An upcoming therapeutic target is the fibroblast growth factor receptor (FGFR) family. However, their prognostic role in head and neck cancer remains unclear.

Objective

To systematically review current evidence on the prognostic value of FGFR family members in head and neck squamous cell carcinoma (HNSCC).

Methods

A systematic search of PubMed, Embase, and the Cochrane Library was performed for publications up to 14 May 2014. Two reviewers screened all articles and included prognostic studies on the molecular biomarkers FGFR1-5 in any type of HNSCC. Relevant studies were assessed on risk of bias using the Quality in Prognostic Studies (QUIPS) tool. Data on FGFR aberrations and survival outcome were extracted from relevant studies. The prognostic value of FGFR aberrations was compared among studies.

Results

The initial search yielded 1568 publications of which 12 fulfilled the inclusion criteria. Four studies reported FGFR1 gene amplification (9.3–17.4 %) and FGFR1 protein overexpression (11.8 %) in HNSCC. FGFR1 protein expression by cancer-associated fibroblasts correlated with poor survival outcome in one study (p < 0.01). Eight studies reported high rates of FGFR4 Gly388Arg polymorphisms (32.5–54.2 %) and FGFR4 protein overexpression (16–35 %), with varying correlations with survival. So far, no studies assessed the prognostic role of FGFR2, FGFR3, or FGFR5 in HNSCC.

Limitations

Significant risk of bias has been identified among included studies. Therefore, cautious interpretation of the results is recommended.

Conclusion

In conclusion, evidence was found for prognostic value of FGFR1 expression in cancer-associated fibroblasts in HNSCC. Prognostic evidence on the other FGFR family members in HNSCC is limited and conflicting. This emphasizes the need for future well-conducted prognostic studies.

Electronic supplementary material

The online version of this article (doi:10.1007/s11523-015-0374-9) contains supplementary material, which is available to authorized users.

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Most cited references 47

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Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives.

Fabrice André, Monica Arnedos, Maria Vittoria Dieci … (2013)

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues.

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The molecular pathogenesis of head and neck squamous cell carcinoma.

S Rothenberg, Leif W. Ellisen (2012)

Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes.

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Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer.

Yong Zhang, Thomas Bachelot, Stephanie Deudon … (2013)

Fibroblast growth factor receptor 1 (FGFR1) and FGFR2 amplifications are observed in approximately 10% of breast cancers and are related to poor outcomes. We evaluated whether dovitinib (TKI258), an inhibitor of FGFR1, FGFR2, and FGFR3, presented antitumor activity in FGFR-amplified breast cancers. Preclinical activity of dovitinib was evaluated in both breast cancer cell lines and an FGFR1-amplified xenograft model (HBCx2). Dovitinib was then evaluated in a phase II trial that included 4 groups of patients with human EGF receptor 2-negative metastatic breast cancer on the basis of FGFR1 amplification and hormone receptor (HR) status. FGFR1 amplification was assessed by silver in situ hybridization. Preplanned retrospective analyses assessed predictive value of FGFR1, FGFR2, and FGF3 amplifications by quantitative PCR (qPCR). Dovitinib monotherapy inhibits proliferation in FGFR1- and FGFR2-amplified, but not FGFR-normal, breast cancer cell lines. Dovitinib also inhibits tumor growth in FGFR1-amplified breast cancer xenografts. Eighty-one patients were enrolled in the trial. Unconfirmed response or stable disease for more than 6 months was observed in 5 (25%) and 1 (3%) patient(s) with FGFR1-amplified/HR-positive and FGFR1-nonamplified/HR-positive breast cancer. When qPCR-identified amplifications in FGFR1, FGFR2, or FGF3 were grouped to define an FGF pathway-amplified breast cancer in HR-positive patients, the mean reduction in target lesions was 21.1% compared with a 12.0% increase in patients who did not present with FGF pathway-amplified breast cancer. Dovitinib showed antitumor activity in FGFR-amplified breast cancer cell lines and may have activity in breast cancers with FGF pathway amplification. ©2013 AACR.

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Author and article information

Contributors

Norbertus A. Ipenburg: norbertipenburg@gmail.com

Koos Koole: K.Koole-2@umcutrecht.nl

K. Seng Liem: sengliem@gmail.com

Pauline M. W. van Kempen: P.M.W.vanKempen-2@umcutrecht.nl

Ron Koole: R.Koole@umcutrecht.nl

Paul J. van Diest: P.J.vanDiest@umcutrecht.nl

Robert J. J. van Es: R.J.J.vanes@umcutrecht.nl

Stefan M. Willems: +31 88 755 6568 , S.M.Willems-4@umcutrecht.nl

Journal

Journal ID (nlm-ta): Target Oncol

Journal ID (iso-abbrev): Target Oncol

Title: Targeted Oncology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1776-2596

ISSN (Electronic): 1776-260X

Publication date (Electronic): 27 June 2015

Publication date PMC-release: 27 June 2015

Publication date (Print): 2016

Volume: 11

Pages: 17-27

Affiliations

[ ]Department of Pathology, University Medical Center Utrecht, PO box 885500, 3508 GA Utrecht, The Netherlands

[ ]Department of Otorhinolaryngology – Head and Neck Surgery, University Medical Center Utrecht, PO box 885500, 3508 GA Utrecht, The Netherlands

[ ]Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, PO box 885500, 3508 GA Utrecht, The Netherlands

[ ]Department of Molecular Carcinogenesis, Netherlands Cancer Institute, PO box 90203, 1006 BE Amsterdam, The Netherlands

Article

Publisher ID: 374

DOI: 10.1007/s11523-015-0374-9

PMC ID: 4759209

PubMed ID: 26115874

SO-VID: bfb67277-12d2-4c89-b7b6-d6630e865120

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review

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Abstract

Background

Objective

Methods

Results

Limitations

Conclusion

Electronic supplementary material

Related collections

Journal of Circulating Biomarkers

Most cited references 47

Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives.

The molecular pathogenesis of head and neck squamous cell carcinoma.

Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer.

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Cited by 12

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