Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Drugs. 2011 Jul 30;71(11):1367-84. doi: 10.2165/11592530-000000000-00000.
Gastric cancer represents one of the most common cancers internationally. Unfortunately the majority of patients still present at an advanced stage, and despite advances in diagnostic and treatment strategies, outcomes still remain poor with high mortality rates despite a decline in incidence. Whilst the utility of classical chemotherapy agents has been explored thoroughly (and continues to be investigated, alone or in various combinations), advances have been slow and the efficacy of these agents has reached a plateau. As such, the focus of recent study has shifted toward developing a greater understanding of the molecular biology of carcinogenesis and the cancer cell phenotype, and, in turn, the development of rationally designed drugs that target molecular aberrancies in signal transduction pathways specific to gastric cancer. These targets include circulating growth and angiogenic factors, cell surface receptors, and other molecules that comprise downstream intracellular signalling pathways, including receptor tyrosine kinases. Therapeutic advances in this area significantly lag behind other solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted therapies in gastric cancer, including rationale and mechanism of action, current and emerging data, as single-agent therapy or in combination regimens. A recently published randomized phaseIII trial supporting the use of trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2)/neu monoclonal antibody, in a selected population of patients is discussed. Therapies that have been evaluated in phase II trials are also reviewed, as well as promising new therapies currently being investigated in preclinical or phase I studies. There is optimism that targeted therapies, whether as single-agent therapy or in combination with traditional therapies, including chemotherapy, radiotherapy and surgery, may yet have an impact on improvement of the overall prognosis of gastric cancer.
胃癌是全球最常见的癌症之一。不幸的是，大多数患者就诊时仍处于晚期，尽管在诊断和治疗策略方面取得了进展，但由于发病率下降，死亡率仍然很高，预后仍然较差。尽管经典化疗药物的疗效已经得到了充分的研究（并且仍在单独或联合各种组合的基础上进行研究），但进展缓慢，这些药物的疗效已经达到了一个平台期。因此，最近的研究重点已经转移到了对癌症发生和癌细胞表型的分子生物学的更深入了解上，并相应地开发出了针对胃癌信号转导通路中特定分子异常的合理设计药物。这些靶点包括循环生长和血管生成因子、细胞表面受体以及构成下游细胞内信号通路的其他分子，包括受体酪氨酸激酶。该领域的治疗进展明显落后于乳腺癌和结直肠癌等其他实体器官恶性肿瘤。本文综述了靶向治疗在胃癌中的作用，包括作用机制和作用机制、当前和新兴的数据、作为单一药物治疗或联合治疗方案。讨论了一项最近发表的支持在选定的患者群体中使用曲妥珠单抗（一种抗人表皮生长因子受体 2（HER2）/neu 单克隆抗体）的随机 III 期试验。还回顾了在 II 期试验中评估的治疗方法，以及目前正在临床前或 I 期研究中进行的有前途的新治疗方法。人们乐观地认为，靶向治疗，无论是作为单一药物治疗还是与传统治疗（包括化疗、放疗和手术）联合使用，都可能对改善胃癌的总体预后产生影响。
