Charalampakis Nikolaos, Elimova Elena, Shimodaira Yusuke, Shiozaki Hironori, Wadhwa Roopma, Ajani Jaffer A
University of Texas M. D. Anderson Cancer Center, Department of Gastrointestinal Medical Oncology , 1515 Holcombe Blvd (FC10.3022), Houston, TX 77030 , USA +1 713 792 2828 ; +1 793 745 1163 ;
Expert Opin Pharmacother. 2015 May;16(7):955-60. doi: 10.1517/14656566.2015.1025750. Epub 2015 Apr 7.
Gastric cancer (GC) continues to be a significant problem worldwide and is the third leading cause of cancer death. Armamentarium to treat GC whether it is potentially curable or metastatic (incurable) has changed little over the last decades with only two new agents being approved (trastuzumab and ramucirumab). Many relatively healthy patients after second-line therapy have limited and generally ineffective options. The recent The Cancer Genome Atlas analysis has uncovered four genotypes of GC; however, it is not sufficient to change our treatment strategies and more work needs to be done. The popular front-line regimen containing a platinum compound and a fluoropyrimidine is widely used for drug development and has worked well globally. Thus, this combination appears suitable for adding a biologic agent. The search for new classes of cytotoxics has almost stopped, but it is clear that cytotoxic therapy continues to contribute and it is here to stay. Biologic agents that modulate the immune system of the host appear promising along with many other biologics that can potentially inhibit signaling pathways that are often employed by GC cells. We will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and MET pathways.
胃癌(GC)在全球范围内仍然是一个重大问题,是癌症死亡的第三大主要原因。在过去几十年里,治疗GC(无论其是潜在可治愈还是转移性(不可治愈))的手段变化不大,仅有两种新药获批(曲妥珠单抗和雷莫西尤单抗)。许多接受二线治疗后的相对健康的患者选择有限且通常效果不佳。最近的癌症基因组图谱分析揭示了GC的四种基因型;然而,这还不足以改变我们的治疗策略,仍需开展更多工作。含铂化合物和氟嘧啶的常用一线方案广泛应用于药物研发,并且在全球范围内效果良好。因此,这种联合方案似乎适合添加一种生物制剂。寻找新型细胞毒性药物的工作几乎已经停止,但很明显细胞毒性疗法仍在发挥作用且将继续存在。调节宿主免疫系统的生物制剂以及许多其他可能抑制GC细胞常用信号通路的生物制剂似乎很有前景。我们将简要介绍针对表皮生长因子受体(EGFR)、雷帕霉素靶蛋白(mTOR)、血管生成和间质上皮转化因子(MET)通路所做的努力。