Kim Hong Jun, Lee Suk-Young, Oh Sang Cheul
Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University Seoul, South Korea.
Front Physiol. 2016 May 9;7:168. doi: 10.3389/fphys.2016.00168. eCollection 2016.
Gastric cancer and colorectal cancer are the leading cause of cancer mortality and have a dismal prognosis. The introduction of biological agents to treat these cancers has resulted in improved outcomes, and combination chemotherapy with targeted agents and conventional chemotherapeutic agents is regarded as standard therapy. Additional newly clarified mechanisms of oncogenesis and resistance to targeted agents require the development of new biologic agents. Aberrant activation of the inositide signaling pathway by a loss of function PTEN mutation or gain of function mutation/amplification of PIK3CA is an oncogenic mechanism in gastric cancer and colorectal cancer. Clinical trials with biologic agents that target the inositide signaling pathway are being performed to further improve treatment outcomes of patients with advanced gastric cancer and metastatic colorectal cancer (CRC). In this review we summarize the inositide signaling pathway, the targeted agents that inhibit abnormal activation of this signaling pathway and the clinical trials currently being performed in patients with advanced or metastatic gastric cancer and metastatic CRC using these targeted agents.
胃癌和结直肠癌是癌症死亡的主要原因，预后不佳。生物制剂用于治疗这些癌症已使治疗效果得到改善，靶向药物与传统化疗药物联合化疗被视为标准疗法。肿瘤发生和对靶向药物耐药的其他新明确机制需要开发新的生物制剂。因PTEN功能缺失突变或PIK3CA功能获得性突变/扩增导致的肌醇磷脂信号通路异常激活是胃癌和结直肠癌的一种致癌机制。目前正在进行针对肌醇磷脂信号通路的生物制剂临床试验，以进一步改善晚期胃癌和转移性结直肠癌（CRC）患者的治疗效果。在本综述中，我们总结了肌醇磷脂信号通路、抑制该信号通路异常激活的靶向药物，以及目前使用这些靶向药物在晚期或转移性胃癌和转移性CRC患者中开展的临床试验。
