Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas

Smilek, Pavel; Neuwirthová, Jana; Jarkovský, Jiří; Dušek, Ladislav; Rottenberg, Jan; Kostřica, Rom; Srovnal, Josef; Hajdúch, Marián; Drábek, Jir̆ı́; Klozar, Jan

doi:10.4149/neo_2012_065

Cited by 39 publications

(27 citation statements)

References 31 publications

(48 reference statements)

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“…By contrast, when EGFR expression was assessed by IHC and real time PCR, a prognostic value for high EGFR expression has been associated with reduced PFS and complete response in cetuximab+RT-treated HNSCC patients, in two studies [73, 74]. …”

Section: Egfr Protein Expressionmentioning

confidence: 99%

“…In another study, a deletion in exon 19 of EGFR was disclosed in two out of 29 HNSCC patients treated with cetuximab and RT. These two patients presented poor clinical outcome, suggesting that this mutation may contribute to the limited response [74]. …”

Section: Egfr Mutationmentioning

confidence: 99%

“…Moreover, EGFRvIII level, detected by real time PCR, was associated with increased DCR but not with time to progression or OS in recurrent or metastatic HNSCC patients treated with erlotinib [91]. However, Smilek et al reported no association between RT-PCR detected EGFRvIII levels and response to cetuximab combined with RT [74]. …”

Section: Egfrviii Expressionmentioning

confidence: 99%

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Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

et al. 2016

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EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression.Considering RT alone, evidence supports the predictive and prognostic role of high EGFR expression only when evaluated by quantitative assays: this may help select the patients who can mostly benefit from accelerated treatment. Conversely, no predictive biomarkers are available when treatment is a combination of surgery, CT and RT. For this combined treatment, several studies indicate that EGFR expression represents a good prognostic parameter only when measured by a “quantitative” or at least semi-quantitative method. With respect to EGFR inhibitors, neither EGFR expression nor increased gene copy number represent prognostic/predictive factors.If validated, nuclear EGFR, TGFα levels, EGFR phopshorylation and polymorphisms could represent additional prognostic factors in relation to combination of surgery, CT and RT, while EGFR polymorphisms and high amphiregulin levels could have prognostic value in patients treated with EGFR inhibitors.

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Section: Egfr Protein Expressionmentioning

confidence: 99%

Section: Egfr Mutationmentioning

confidence: 99%

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Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

et al. 2016

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“…[24][25][26] This mutation is most prevalent in malignant gliomas (20-30% in unselected patients with a glioblastoma multiforme [GBM] and 50-60% in patients whose tumors show amplification of wild-type EGFR). 27 Recent studies identified EGFRvIII in head and neck squamous cell carcinomas (~21%), 28 squamous cell carcinomas of the lung (~5%), 29,30 and breast (~5%), 31 suggesting broader implications to human cancer. 32 EGFRvIII is known to contribute to radio resistance of tumor cells 33 at least in part through enhanced repair of DNA doublestrand breaks.…”

Section: Egfrviiimentioning

confidence: 99%

EGFR signaling and autophagy dependence for growth, survival, and therapy resistance

Jutten

Rouschop

2013

Cell Cycle

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“…Mutational activation of KRAS only occurred in 2.6 % of 115 clinical specimens of SCCHN, although copy number amplification of KRAS was found in 10 samples (8.7 %) in the same study [229]. In another study, KRAS mutations were found in 4 out of 29 patients with SCCHN and the presence of the G12V KRAS mutation was associated with an absence of response to cetuximab and radiotherapy [230].…”

Section: Kras Mutationmentioning

confidence: 96%

EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

Liu

Cracchiolo

Beck

et al. 2014

Molecular Determinants of Head and Neck Cancer

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Squamous cell carcinoma of the head and neck (SCCHN) is one of the more challenging cancers to treat. Although great progress has been made over the years, available treatment options are still far from ideal, as epitomized by a 5-year survival rate of only 30-40 %. A unique feature of SCCHN is that elevated expression of the epidermal growth factor receptor (EGFR), a member of the ErbB receptor tyrosine kinase (RTK) family and highly relevant to oncogenic proliferation, occurs in a significant number of cases, which has prompted great interest in utilizing EGFR-targeted therapies to treat this devastating disease. Significant advances in the treatment of SCCHN have been made using EGFR-targeting monoclonal antibodies. Another class of EGFR-targeting inhibitors, tyrosine kinase inhibitors (TKIs), has also shown promise as a potential treatment option. In order to appreciate how these therapeutic agents work and why they fail when they do, it is crucial to explore the biology of the ErbB family members, the signaling pathways that are associated with them, and how they interact with each specific therapeutic agent. This chapter discusses the biology of EGFR and other ErbB family members in SCCHN, and summarizes the current status of the application of EGFR and ErbB inhibitors.Keywords Epidermal growth factor receptor (EGFR) · Squamous cell carcinoma of the head and neck (SCCHN) · Tyrosine kinase inhibitor (TKI) · Monoclonal antibodies · Erlotinib · Cetuximab · Radiation · Cisplatin · ErbB family

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Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas

Cited by 39 publications

References 31 publications

Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

EGFR signaling and autophagy dependence for growth, survival, and therapy resistance

EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

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