University of Torino, Department of Oncology, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale 142, 10060 Candiolo, Torino, Italy.
Trends Mol Med. 2016 Jul;22(7):534-544. doi: 10.1016/j.molmed.2016.05.004. Epub 2016 May 31.
Gastric cancer is the third greatest global cause of cancer-related deaths. Despite its high prevalence, only recently have comprehensive genomic surveys shed light on its molecular alterations. As surgery is the only curative treatment strategy and chemotherapy has shown limited efficacy, new treatments are urgently needed. Many molecular therapies for gastric cancer have entered clinical trials but-apart from Trastuzumab and Ramucirumab-all have failed. We analyze the current knowledge of the genetic 'landscape' of gastric cancers, elaborating on novel, preclinical approaches. We posit that this knowledge lays the basis for identifying bona fide molecular targets and developing solid therapeutic approaches, requiring accurate patient selection and taking advantage of preclinical models to assist clinical development of novel combination strategies.
胃癌是全球导致癌症死亡的第三大主要原因。尽管其发病率很高，但直到最近，全面的基因组调查才揭示了其分子改变。由于手术是唯一的治愈性治疗策略，而化疗的疗效有限，因此迫切需要新的治疗方法。许多胃癌的分子疗法已经进入临床试验，但除了曲妥珠单抗和雷莫芦单抗外，所有这些疗法都失败了。我们分析了目前对胃癌遗传“景观”的认识，阐述了新的、临床前的方法。我们认为，这些知识为确定真正的分子靶点和开发有效的治疗方法奠定了基础，这需要对患者进行准确的选择，并利用临床前模型来辅助新的联合策略的临床开发。
