- 期刊
The HGF/c-Met/COX-2 and Jagged1/Notch1/COX-2 Pathways as Molecular Targets for Gastric Cancer Treatment
HGF/c-Met/COX-2和Jagged1/Notch1/COX-2路徑為胃癌治療之分子標靶
摘要
在2012年的台灣，胃癌在所有癌症死亡率中排名第五位。雖然在最近的數十年間，胃癌的病患數量逐年遞減，但其在全世界的癌症死亡率中仍是排名第二。因此，迫切地需要發展更多具有潛力的分子標靶和治療方式來治療胃癌病患。臨床上，COX-2的大量表現與胃癌的轉移、侵犯和血管新生有高度地關係。在胃癌中也發現COX-2和c-Met（或Jagged1）的表現量呈現正相關。在許多研究中也指出，HGF/c-Met和Jagged1/Notch1路徑能促進COX-2的表現，進而促進胃癌細胞的生長、移動和侵犯。最近，針對HGF/c-Met路徑已設計有許多單株抗體或受體酪氨酸激?抑制劑，且在許多臨床試驗顯示出有治療胃癌之潛力。因此，此文章整合了HGF/c-Met/COX-2和Jagged1/Notch1/COX-2路徑的分子機制，以及最新的胃癌標靶治療。
並列摘要
In Taiwan, gastric cancer ranked fifth in total cancer mortality in 2012. Although the number of gastric cancer cases has declined in recent decades, it is still the second leading cause of cancer mortality worldwide. Therefore, more potential molecular targets and therapeutic options for gastric cancer treatment are urgently needed. The overexpression of COX-2 has been shown to be highly associated with metastasis, invasion and angiogenesis of gastric cancer. A positive correlation between COX-2 and c-Met (or Jagged1) expression also has been found in gastric cancer. Moreover, several studies indicated that hepatocyte growth factor (HGF)/c-Met and Jagged1/Notch1 pathways can up-regulate COX-2 expression, resulting in increased cell growth, migration and invasion in gastric cancer cells. Recently, various monoclonal antibodies or receptor tyrosine kinase inhibitors have been designed to target HGF/c-Met pathway and have shown potentials for gastric cancer therapy in clinical trials. In this article, we have summarized the molecular mechanisms of HGF/c-Met/COX-2 and Jagged1/ Notch1/COX-2 pathways, and the latest target therapies for gastric cancer.