Abstract
Target therapies and notably monoclonal antibodies are currently being considered for esophageal, gastric, and gastroesophageal junction cancers. EGFR was found to be overexpressed in 60-86% of gastric or gastroesophageal tumors and in 50-70% of esophageal cancers. Cetuximab was shown to be a radiosensitizing agent in the treatment of ENT neoplasia. These results led to several phase II encouraging therapeutic trials evaluating the combination of cetuximab with radiochemotherapy in locally advanced esophageal cancers. Numerous encouraging phase II trials evaluating cetuximab combined with chemotherapy in patients with gastric adenocarcinoma or gastroesophageal junction cancer were reported. These promising results are still to be confirmed by the ongoing phase III trials. Several studies reported HER2 overexpression in gastric cancer (7-34%), which appeared to be associated with poorer prognosis. Trastuzumab is a monoclonal antibody directed against the extracellular HER2 domain. The international phase III trial known as ToGA (Trastuzumab for Gastric Cancer) aimed to determine the clinical efficacy and acceptable toxicity profile of trastuzumab in combination with first-line chemotherapy in HER2-overexpressing gastric or gastroesophageal cancer. Angiogenesis is an essential step in the initial phase of tumorigenesis, and it is normally absent from healthy tissues except for particular physiological situations, such as wound healing. VEGF-A plays a role in endothelial growth and angiogenesis. Bevacizumab, a humanized monoclonal anti-VEGF-A antibody, is currently being studied for gastric cancer. The phase III AVAGAST study, evaluating bevacizumab in association with chemotherapy in advanced gastric adenocarcinoma, did not achieve its primary aim of improved OS in bevacizumab-treated patients.
Keywords: Esophageal cancer, gastric cancer, gastroesophageal cancer, target therapies, monoclonal antibodies
Current Topics in Medicinal Chemistry
Title:Targetting Esophageal and Gastric Cancers with Monoclonal Antibodies
Volume: 12 Issue: 15
Author(s): Emmanuelle Norguet, Laetitia Dahan and Jean-Francois Seitz
Affiliation:
Keywords: Esophageal cancer, gastric cancer, gastroesophageal cancer, target therapies, monoclonal antibodies
Abstract: Target therapies and notably monoclonal antibodies are currently being considered for esophageal, gastric, and gastroesophageal junction cancers. EGFR was found to be overexpressed in 60-86% of gastric or gastroesophageal tumors and in 50-70% of esophageal cancers. Cetuximab was shown to be a radiosensitizing agent in the treatment of ENT neoplasia. These results led to several phase II encouraging therapeutic trials evaluating the combination of cetuximab with radiochemotherapy in locally advanced esophageal cancers. Numerous encouraging phase II trials evaluating cetuximab combined with chemotherapy in patients with gastric adenocarcinoma or gastroesophageal junction cancer were reported. These promising results are still to be confirmed by the ongoing phase III trials. Several studies reported HER2 overexpression in gastric cancer (7-34%), which appeared to be associated with poorer prognosis. Trastuzumab is a monoclonal antibody directed against the extracellular HER2 domain. The international phase III trial known as ToGA (Trastuzumab for Gastric Cancer) aimed to determine the clinical efficacy and acceptable toxicity profile of trastuzumab in combination with first-line chemotherapy in HER2-overexpressing gastric or gastroesophageal cancer. Angiogenesis is an essential step in the initial phase of tumorigenesis, and it is normally absent from healthy tissues except for particular physiological situations, such as wound healing. VEGF-A plays a role in endothelial growth and angiogenesis. Bevacizumab, a humanized monoclonal anti-VEGF-A antibody, is currently being studied for gastric cancer. The phase III AVAGAST study, evaluating bevacizumab in association with chemotherapy in advanced gastric adenocarcinoma, did not achieve its primary aim of improved OS in bevacizumab-treated patients.
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Cite this article as:
Norguet Emmanuelle, Dahan Laetitia and Seitz Jean-Francois, Targetting Esophageal and Gastric Cancers with Monoclonal Antibodies, Current Topics in Medicinal Chemistry 2012; 12 (15) . https://dx.doi.org/10.2174/156802612803531360
DOI https://dx.doi.org/10.2174/156802612803531360 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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