Combining Targeted Agents: Blocking the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

Sandler, Alan; Herbst, Roy S.

doi:10.1158/1078-0432.ccr-06-0796

Cited by 67 publications

(38 citation statements)

References 18 publications

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“…For example, bevacizumab or pemetrexed are not available for SCC therapy, although bevacizumab is one of the few drugs found to significantly impact lung cancer survival (30,31). Johnson et al reported that some SCC patients treated with bevacizumab experienced severe pulmonary hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma

Miyamae

Shimizu

Hirato³

et al. 2011

Oncol Rep

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Abstract. Epidermal growth factor receptor (EGFR) gene mutations have been reported to be clinically significant in non-small cell lung cancer (NSCLC). However, because most previous studies focused only on adenocarcinomas, EGFR mutations in other histotypes are poorly investigated. We evaluated the frequency of EGFR gene mutations in squamous cell carcinoma (SCC) and its clinicopathological features. In total, 89 frozen tumor specimens that had been first diagnosed as SCCs, were examined for EGFR mutations in exons 19 and 21 using direct sequencing, PNA-enriched sequencing and SmartAmp2. Additionally, pathological investigation, including immunostaining for p63 and TTF-1, alcian blue staining and EGFR mutation-specific immunohistochemistry in mutation-positive samples was also performed. The frequency of EGFR mutations was 5.6% (5/89); all mutations were deletions in EGFR exon 19. Immunohistological investigation of these samples revealed that two of five were positive for p63 and TTF-1 staining, and showed production of mucin, as evidenced by alcian blue staining. Consequently, three of the samples were considered to be true SCC at final pathological diagnosis, while the remaining two samples were revised to adenosquamous carcinoma and adenocarcinoma. The final frequency of the EGFR mutations in true SCC was 3.4% (3/87). In conclusion, EGFR mutations were found in a small, but significant, number of SCC tumor samples and thus EGFR mutational analysis was useful in the accurate diagnosis of SCC. Our data demonstrate that EGFR mutational analysis should be performed not only in adenocarcinoma, but also in SCC to allow accurate diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma

Miyamae

Shimizu

Hirato³

et al. 2011

Oncol Rep

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“…Bevacizumab is licensed for use in combination with fluorouracil-based chemotherapy for the first-line treatment of patients with metastatic colorectal cancer in the United States and Europe (9). Recently, the clinical use of bevacizumab combined with paclitaxel in the treatment of advanced NSCLC has shown exciting results (13,14).…”

Section: Introductionmentioning

confidence: 99%

Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma

Fujita¹,

Sano²,

Kimura³

et al. 2007

Oncol Rep

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Abstract. Human tumors are dependent on angiogenesis for growth, and the vascular endothelial growth factor (VEGF) is a major regulator of this process. Bevacizumab (Avastin ® ), a monoclonal antibody directed against VEGF, has shown promise in treating a variety of cancers. In this study, we first examined the anti-tumor effects of bevacizumab on head and neck squamous cell carcinoma (HNSCC). Then we examined the effects of bevacizumab combined with paclitaxel, a chemotherapeutic agent, in HNSCC. This is the first demonstration of the anti-tumor effects of bevacizumab on HNSCC. In vitro, bevacizumab did not show any antiproliferative effects against the HNSCC cell lines. However, in vivo, bevacizumab showed dramatic anti-tumor effects against HNSCC tumor xenografts in mice. In addition, treatment with a bevacizumab-paclitaxel combination resulted in a remarkable inhibition of the HNSCC tumor xenografts, compared to the effects of each agent separately. A decreased blood vessel density and an increased apoptotic index were seen in the shrunken tumors. These results suggest that bevacizumab in combination with paclitaxel could have useful clinical application in HNSCC.

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“…[3][4][5] Indeed, Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (Avastin, Genentech), in combination with a standard platin-based chemotherapy regiment has been shown to improve overall survival and delay the time to progression in patients with advanced non-small cell lung cancer, making Bevacizumab one of the few drugs to significantly impact lung cancer survival. 6,7 However, a randomized phase II study conducted by Johnson et al showed some patients with squamous cell carcinoma (SQCC) experienced life-threatening pulmonary hemorrhage. 8 These results have even led to the exclusion of SQCC cases from ongoing or new phase III studies.…”

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confidence: 99%

The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

Savcı-Heijink

Kosari

Aubry

et al. 2009

The American Journal of Pathology

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Results from several microarray-based studies have led to the identification of up-regulated expression levels of the DSG3 gene in pulmonary squamous cell carcinomas (SQCCs). The purpose of this study was to determine the role of DSG3 expression in the diagnosis of SQCCs of the lung and to compare DSG3 with p63, CK5, and CK6, as markers of squamous cell differentiation. Expression of DSG3 mRNA was evaluated in bulk laser capture microdissection-derived microarray data and by quantitative reverse transcription PCR on both SQCCs and adenocarcinomas. Expression levels of p63, CK5, and CK6 were evaluated in microarray data from the same set. An immunohistochemical study using antibodies directed against DSG3, p63, and CK5/6 was also performed. DSG3 was over-expressed in SQCCs but had very limited expression in both adenocarcinomas and nonneoplastic lungs. The microarray data showed that DSG3 had a sensitivity and specificity of 88% and 98%, respectively, in detecting SQCC versus adenocarcinoma. In comparison, sensitivity and specificity was 92% and 82% for p63, and 85% and 96% for CK5, respectively. The correlation coefficient between the microarray and immunohistochemical data for these genes was greater than or equal to 0.9. Using immunohistochemistry , sensitivity and specificity of DSG3 for lung cancers were 98% and 99% , respectively. Therefore , DSG3 can be a useful ancillary marker to separate SQCC from other subtypes of lung cancer.

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Combining Targeted Agents: Blocking the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

Cited by 67 publications

References 18 publications

Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma

Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma

Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma

The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

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