Role of Targeted Therapy in Gastric Cancer
Radwa Mohammed Hamed;
Abstract
Gastric cancer is the second leading cause of death from malignant disease worldwide, with especially high mortality rates in East, South, and Central Asia; Central and Eastern Europe; and South America. Gastric cancers are most frequently discovered in advanced stages, except in East Asia, where screening programs have been established. The prognosis of advanced gastric cancer remains poor, and curative surgery is regarded as the only option for cure. Early detection of resectable gastric cancer is extremely important for good patient outcomes; therefore, technologically sophisticated screening programs are needed (Derici et al., 2011).
Over the past two decades, efforts have been made to improve surgical techniques, adjuvant chemotherapy, preoperative chemotherapy and radiation. However, gastric cancer remains difficult to cure, with very poor prognosis due to systemic recurrence after curative surgical resection (Saghier et al., 2013).
The commonly used combination chemotherapy regimens, consisting of a fluoropyrimidine plus a platinum agent with or without docetaxel or anthracyclines (Wagner et al., 2010).
The emergence of new chemotherapy agents and targeted therapies, together with increasing knowledge of biological pathways underlying GC and the ability to predict which patients or tumors will respond to which treatment, may lead to improved GC patient outcomes (Power et al., 2010).
One of the most considerable innovative targets in human cancer is the human epidermal growth factor receptor (EGFR) family. Relatively to HER2, this is highly expressed in a significant proportion of GC and thus it is nowadays considered an excellent therapeutic target. Gastric cancer harboring HER2 overexpression was shown to have a worse prognosis. The HER2 overexpression more commonly seen in the intestinal-type than diffuse-type cancers (Janjigian et al., 2012).
In the trastuzumab for gastric cancer (ToGA) trial, trastuzumab, a recombinant humanized monoclonal antibody that targets the extracellular domain of the HER2 protein, was evaluated in HER2 overexpressing gastric and gastroesophageal junction cancer. Trastuzumab in combination with (5-FU/capecitabine plus cisplatin) improved the OS (13.8 mo in trastuzumab arm VS 11.1 mo in chemotherapy arm), also the median PFS was increased with the addition of transtuzumab to standard chemotherapy: 6.7 mo in the transtuzumab arm VS 5.5 mo in the chemotherapy arm. So, trastuzumab was approved by the Food and Drug Administration and the European Medicines Agency (EMA) for patients with HER2-positive metastatic GC or GEJ who have not received previous anticancer therapy for metastatic disease (De Mello et al., 2013).
Over the past two decades, efforts have been made to improve surgical techniques, adjuvant chemotherapy, preoperative chemotherapy and radiation. However, gastric cancer remains difficult to cure, with very poor prognosis due to systemic recurrence after curative surgical resection (Saghier et al., 2013).
The commonly used combination chemotherapy regimens, consisting of a fluoropyrimidine plus a platinum agent with or without docetaxel or anthracyclines (Wagner et al., 2010).
The emergence of new chemotherapy agents and targeted therapies, together with increasing knowledge of biological pathways underlying GC and the ability to predict which patients or tumors will respond to which treatment, may lead to improved GC patient outcomes (Power et al., 2010).
One of the most considerable innovative targets in human cancer is the human epidermal growth factor receptor (EGFR) family. Relatively to HER2, this is highly expressed in a significant proportion of GC and thus it is nowadays considered an excellent therapeutic target. Gastric cancer harboring HER2 overexpression was shown to have a worse prognosis. The HER2 overexpression more commonly seen in the intestinal-type than diffuse-type cancers (Janjigian et al., 2012).
In the trastuzumab for gastric cancer (ToGA) trial, trastuzumab, a recombinant humanized monoclonal antibody that targets the extracellular domain of the HER2 protein, was evaluated in HER2 overexpressing gastric and gastroesophageal junction cancer. Trastuzumab in combination with (5-FU/capecitabine plus cisplatin) improved the OS (13.8 mo in trastuzumab arm VS 11.1 mo in chemotherapy arm), also the median PFS was increased with the addition of transtuzumab to standard chemotherapy: 6.7 mo in the transtuzumab arm VS 5.5 mo in the chemotherapy arm. So, trastuzumab was approved by the Food and Drug Administration and the European Medicines Agency (EMA) for patients with HER2-positive metastatic GC or GEJ who have not received previous anticancer therapy for metastatic disease (De Mello et al., 2013).
Other data
| Title | Role of Targeted Therapy in Gastric Cancer | Other Titles | دور العلاج الموجه في أورام المعدة | Authors | Radwa Mohammed Hamed | Issue Date | 2014 |
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