a Department Oncology , University Hospital of Udine , Udine , Italy.
b Department of Medical Area , University of Udine , Udine , Italy.
Expert Rev Clin Pharmacol. 2017 Jun;10(6):609-619. doi: 10.1080/17512433.2017.1313113. Epub 2017 Apr 10.
The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.
免疫疗法的广泛应用正在彻底改变许多实体瘤的治疗模式。尽管化疗仍然是晚期胃癌的治疗基础,但对其分子特征的认识不断提高,对其潜在生物学的理解也不断深入,这为新型免疫疗法的临床发展提供了支持。然而,最近测试这些新药物的临床试验结果提出了一个问题,即如何识别那些可能从中大大受益的患者。
本文总结了目前对胃癌不同临床特征的生物学和机制的理解。特别是,经过全面的文献检索,我们推测是否有特定的患者分子亚型可以从免疫疗法中获得更多益处。
大多数癌症可能会逃避免疫反应,而免疫反应通常是由激活和抑制信号之间的微妙平衡来调节的。例如,CTLA-4 和 PD-1 一旦与 PD-L1/2 结合,都可能抑制 T 细胞信号。利用药物来利用免疫系统的力量似乎是胃癌治疗的终极前沿。虽然抗 CTLA-4 抗体的活性较低,但 PD1/-L1 抑制剂的疗效证据越来越多。寻找免疫疗法的预测因素将为这些药物的最佳使用提供关键线索。