The progress of targeted therapy in advanced gastric cancer
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REVIEW
Open Access
The progress of targeted therapy in advanced gastric cancer Miao-zhen Qiu and Rui-hua Xu*
Abstract Although palliative chemotherapy has been shown to prolong survival and improve quality of life, the survival of advanced gastric cancer (AGC) patients remains poor. With the advent of targeted therapy, many molecular targeted agents have been evaluated in clinical studies. Trastuzumab, an anti-HER2 monoclonal antibody, has shown activity against HER2-positive AGC and becomes the first targeted agent approved in AGC. Drugs that target epidermal growth factor receptor, including monoclonal antibody and tyrosine kinase inhibitor, do not bring survival benefit to patients with AGC. Additionally, vascular endothelial growth factor inhibitors are also under investigation. Ramucirumab has shown promising result. Other targeted agents are in preclinical or early clinical development, such as mammalian target of rapamycinm inhibitors and c-MET inhibitors.
Introduction Approximately one million people are diagnosed each year with gastric cancer, making it the fourth most common cancer and the second leading cause of cancer related death worldwide with an estimated 800,000 deaths caused by the disease [1]. The incidence of gastric cancer varies widely according to geographic region and is particularly common in eastern Asia [2]. According to the 2012 Chinese cancer registry annual report, gastric cancer is the third most common cancer and the second leading cause of cancer related death in China [3]. The only treatment that offers a potential cure is complete resection of the tumor. However, in most of countries, the majority of patients are diagnosed at advanced stages and have a poor prognosis. Though first-line chemotherapy for advanced gastric cancer (AGC) prolongs overall survival (OS) and improves quality of life compared with best supportive care (BSC). The median survival of advanced gastric cancer patients who received palliative chemotherapy is approximately 7 to 11 months [4-8]. In 2010, trastuzumab (Herceptin, Roche, Basel, Switzerland), a recombinant humanized monoclonal antibody that targets human epidermal growth factor receptor-2 (HER2), had already been confirmed to be * Correspondence: [email protected] Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou 510060, China
effective when combined with chemotherapy in HER2positive AGC patients [9]. Trastuzumab is the first targeted agent that gets the indication in AGC, but it is not the only targeted agents which have tried their applications in AGC. The other therapeutic strategies include: epidermal growth factor receptor (EGFR) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, hepatocyte growth factor (HGF) and its receptor c-MET pathway inhibitor, mammalian target of rapamycinm (m-TOR) inhibitor et al. This review will focus on the recent progress in targeted agents fo
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