Division of Hematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, Hong Kong.
Oncologist. 2012;17(3):346-58. doi: 10.1634/theoncologist.2011-0311. Epub 2012 Feb 14.
Gastric cancer is one of the leading causes of cancer death. With greater understanding of the molecular basis of carcinogenesis, targeted agents have led to a modest improvement in the outcome of advanced gastric cancer (AGC) patients.
We conducted an overview of the published evidence regarding the use of targeted therapy in AGC patients. Thus far, the human epidermal growth factor receptor (HER) pathway, angiogenic pathway, and phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin pathway have emerged as potential avenues for targeted therapy in AGC patients. The promising efficacy results of the Trastuzumab for Gastric Cancer trial led to the approved use of trastuzumab-based therapy as first-line treatment for patients with HER-2+ AGC. On the other hand, the Avastin® in Gastric Cancer trial evaluating bevacizumab in combination with chemotherapy did not meet its primary endpoint of a longer overall survival duration despite a significantly higher response rate and longer progression-free survival time in patients in the bevacizumab arm. Phase III data are awaited for other targeted agents, including cetuximab, panitumumab, lapatinib, and everolimus.
Recent progress in targeted therapy development for AGC has been modest. Further improvement in the outcome of AGC patients will depend on the identification of biomarkers in different patient populations to facilitate the understanding of gastric carcinogenesis, combining different targeted agents with chemotherapy, and unraveling new molecular targets for therapeutic intervention.
胃癌是癌症死亡的主要原因之一。随着对致癌分子基础的深入了解，靶向药物的应用使晚期胃癌（AGC）患者的治疗效果得到了一定程度的改善。
我们对靶向治疗在 AGC 患者中的应用进行了文献综述。迄今为止，人类表皮生长因子受体（HER）通路、血管生成通路和磷脂酰肌醇-3-激酶（PI3K）-Akt-雷帕霉素哺乳动物靶点（mTOR）通路已成为 AGC 患者靶向治疗的潜在途径。曲妥珠单抗治疗胃癌试验的有前景的疗效结果导致批准曲妥珠单抗为 HER-2+ AGC 患者的一线治疗。另一方面，评估贝伐珠单抗联合化疗在胃癌中的应用的 Avastin® in Gastric Cancer 试验尽管贝伐珠单抗组患者的总生存期更长，且无进展生存期更长，但未达到延长总生存期的主要终点。其他靶向药物，包括西妥昔单抗、帕尼单抗、拉帕替尼和依维莫司的 III 期数据正在等待中。
晚期胃癌靶向治疗的发展进展有限。要进一步改善 AGC 患者的治疗效果，取决于不同患者人群中生物标志物的鉴定，以促进对胃癌发生机制的理解，将不同的靶向药物与化疗相结合，并揭示新的治疗靶点。
