Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma

Löffler‐Ragg, Judith; Witsch‐Baumgartner, Martina; Tzankov, Alexandar; Hilbe, Wolgang; Schwentner, Ilona; Sprinzl, Georg Mathias; Utermann, Gerd; Zwierzina, Heinz

doi:10.1016/j.ejca.2005.08.034

Cited by 146 publications

(107 citation statements)

References 19 publications

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“…The present study is in agreement with some authors who have also reported the absence or low incidence of EGFR mutations in HNSCC [19][20][21]. It has been noticed that EGFR mutations are also rare or absent in cancers other than lung cancer.…”

Section: Discussionsupporting

confidence: 82%

Mutations in the tyrosine kinase domain of the EGFR gene are rare in the Korean Oral Squamous Cell Carcinoma

Lee¹

2016

Journal of the Korea Society of Computer and Information

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The epidermal growth factor receptor(EGFR) protein kinase signaling is an important pathway in cancer development and recently reported that EGFR and its kinase domain molecules are mutated in various of cancers including head and neck cancer. Functional deregulation of EGFR due to mutations in coding exons and copy number amplification is the most common event in cancers, especially among receptor tyrosine kinases(TK). We have analyzed Korean oral squamous cell carcinomas (OSCC) cell lines for mutations in EGFRTK. Exons encoding the hot-spot regions in the TK domain of EGFR (exons 17 to 23) were amplified by using polymerase chain reaction(PCR) and sequenced directly. EGFR expression was also analyzed in 8 OSCC cell lines using western blotting. Data analysis of the EGFR exons 17 to 23 coding sequences did not show any mutations in the 8 OSCC cell lines that were analyzed. The absence of mutations indicate that protein overexpression might be responsible for activation rather than mutation.

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Section: Discussionsupporting

confidence: 82%

Mutations in the tyrosine kinase domain of the EGFR gene are rare in the Korean Oral Squamous Cell Carcinoma

Lee¹

2016

Journal of the Korea Society of Computer and Information

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“…In contrast, EGFR kinase domain mutations were rare among US (zero out of 65) or European (one out of 100) SCCHN cases (Cohen et al, 2005a;Loeffler-Ragg et al, 2006). Interestingly, one gefitinib-responsive SCCHN patient harboured a heterozygous mutation within ErbB2 (V773A) (Cohen et al, 2005a).…”

Section: Targeting Epidermal Growth Factor-receptor Signalling In Scchnmentioning

confidence: 99%

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

2007

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Despite significant advances in the use of surgery, chemotherapy and radiotherapy to treat squamous cell carcinoma of the head and neck (SCCHN), prognosis has improved little over the past 30 years. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of SCCHN disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. The epidermal growth factor receptor (EGFR) is expressed at much higher levels in SCCHN tumours than in normal epithelial tissue, and EGFR expression correlates with poor prognosis. Therefore, much effort is currently directed toward targeting aberrant EGFR activity (e.g. cell signalling) in SCCHN. This review discusses the efficacy of novel therapies targeting the EGFR (e.g. anti-EGFR antibodies and EGFR tyrosine kinase inhibitors) that are currently tested in SCCHN patients.

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“…About sensitivity of EGFR tyrosine kinase inhibitors such as gefitinib, the effect of an activating mutation and an inactivating mutation of the intracellular domain of EGFR have been reported (29)(30)(31)(32)(33). Acquired resistance was associated with the emergence of a second mutation in EGFR (a methionine for threonine substitution at amino acid T790M) (31,34,35).…”

Section: -------------------------------------------------mentioning

confidence: 99%

Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma

et al. 2010

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Abstract. The epidermal growth factor receptor (EGFR) and a related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. Heterodimerization of EGFR and HER-2 has been known to create intense proliferative signals. Lapatinib (GW572016) is a small molecule that is administrated orally and functions as a reversible inhibitor of both EGFR and HER-2 tyrosine kinases. In the present study, we evaluated the antitumor effect of lapatinib on head and neck squamous cell carcinoma (HNSCC) cell lines in vitro and in vivo. In vivo we examined the antitumor effects of combined treatment with lapatinib and either cisplatin or paclitaxel. In vitro lapatinib displayed antiproliferative effects on HNSCC cells. The IC 50 of lapatinib ranged between 13.6 and 60.2 μM after 24-h exposure to lapatinib. A correlation was not observed between results of in vitro proliferation assays for lapatinib and the expression of EGFR or HER-2. In vivo lapatinib displayed antitumor activity, and induced apoptosis in nude mice bearing an established xenograft of YCU-H891 cells. Lapatinib did not significantly inhibit angiogenesis. Combination treatment of lapatinib with cisplatin or paclitaxel enhanced antitumor activity mainly by inducing apoptosis. Inhibition of antiangiogenesis was observed only for combination treatment of lapatinib with paclitaxel (compared to vehicle control). These results suggest that: i) lapatinib has antitumor effects in vitro and in vivo; ii) lapatinib may be more effective in combination with cisplatin or paclitaxel; and iii) lapatinib might provide useful clinical benefits to HNSCC patients.

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Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma

Cited by 146 publications

References 19 publications

Mutations in the tyrosine kinase domain of the EGFR gene are rare in the Korean Oral Squamous Cell Carcinoma

Mutations in the tyrosine kinase domain of the EGFR gene are rare in the Korean Oral Squamous Cell Carcinoma

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma

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