Indiana University School of Medicine, Department of Medicine , 535 Barnhill Dr RT 473, Indianapolis, IN 46202 , USA
Expert Opin Investig Drugs. 2014 Feb;23(2):273-8. doi: 10.1517/13543784.2014.876408. Epub 2013 Dec 30.
Cancer develops mainly as a result of accumulating mutations in genes controlling cell growth regulation. RAS is one of the most commonly mutated genes in cancer. While agents targeting the signaling aspects of RAS have met with some success, resistance to therapy remains a major issue. Another focus of drug development has been to harness the immune system to target cells harboring mutated proteins, which can appear 'foreign' to the immune system. It has been observed that cancer is able to avoid regular immune surveillance through local and systemic mechanisms leading to immune tolerance. One potential way of breaking immune tolerance is through vaccine therapy.
The authors review the current but limited available literature on KRAS vaccine therapy. The research reviewed was identified from PubMed and presentations from national oncology meetings related to KRAS vaccines in general and GI-4000 series specifically.
While targeting KRAS has proven difficulties, developing novel vaccine approaches such as 'tarmogens' appear to be safe with early efficacy in subset of patients with KRAS mutations. However, further research is crucial to identify this group of patients and develop biomarkers.
癌症主要是由于控制细胞生长调节的基因发生突变而发展的。RAS 是癌症中最常发生突变的基因之一。虽然靶向 RAS 信号通路的药物已经取得了一些成功，但对治疗的耐药性仍然是一个主要问题。药物开发的另一个重点是利用免疫系统来靶向携带突变蛋白的细胞，这些细胞对免疫系统来说可能是“外来的”。已经观察到，癌症通过导致免疫耐受的局部和全身机制逃避常规免疫监测。打破免疫耐受的一种潜在方法是通过疫苗治疗。
作者回顾了目前关于 KRAS 疫苗治疗的有限可用文献。综述中所涉及的研究是从 PubMed 以及与 KRAS 疫苗（一般而言）和 GI-4000 系列（具体而言）相关的全国肿瘤会议的演讲中确定的。
虽然靶向 KRAS 已被证明存在困难，但开发新型疫苗方法，如“tarmogens”，似乎对具有 KRAS 突变的患者亚群安全且早期有效。然而，进一步的研究至关重要，以确定这组患者并开发生物标志物。
