BACKGROUND: Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed. SUMMARY: The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. KEY MESSAGE: The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways. PRACTICAL IMPLICATIONS: Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under development.
BACKGROUND:Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed. SUMMARY: The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. KEY MESSAGE: The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways. PRACTICAL IMPLICATIONS: Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under development.
Authors: B F El-Rayes; M Zalupski; T Bekai-Saab; L K Heilbrun; N Hammad; B Patel; S Urba; A F Shields; U Vaishampayan; S Dawson; K Almhanna; D Smith; P A Philip Journal: Ann Oncol Date: 2010-03-23 Impact factor: 32.976
Authors: M Moehler; A Mueller; J T Hartmann; M P Ebert; S E Al-Batran; P Reimer; M Weihrauch; F Lordick; T Trarbach; S Biesterfeld; M Kabisch; D Wachtlin; P R Galle Journal: Eur J Cancer Date: 2011-05-09 Impact factor: 9.162
Authors: M Moehler; A Mueller; T Trarbach; F Lordick; T Seufferlein; S Kubicka; M Geißler; S Schwarz; P R Galle; S Kanzler Journal: Ann Oncol Date: 2010-11-30 Impact factor: 32.976
Authors: Marwa Matboli; Sarah El-Nakeep; Nourhan Hossam; Alaa Habieb; Ahmed E M Azazy; Ali E Ebrahim; Ziad Nagy; Omar Abdel-Rahman Journal: World J Gastroenterol Date: 2016-07-14 Impact factor: 5.742