Yu Juehua, Liu Shi-He, Sanchez Robbi, Nemunaitis John, Rozengurt Enrique, Brunicardi F Charles
Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
Mary Crowley Cancer Research Center, Dallas, TX, USA.
Surgeon. 2017 Feb;15(1):24-29. doi: 10.1016/j.surge.2016.05.002. Epub 2016 Jun 28.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with an overall 5-year survival rate less than 5% due to the poor early diagnosis and lack of effective therapeutic options. The most effective therapy remains surgery, however post-operative survival could be enhanced with effective adjuvant therapy. The massive information gained from Omics techniques on PDAC at the beginning of the 21st century is a remarkable accomplishment. However, the information gained from the omics data, including next generation sequencing data, has yet to successfully affect care of patients suffering with PDAC. Therefore, we propose the development of an actionable genomic platform that matches a patient's PDAC clinically actionable genes with potential targeted adjuvant therapies. Using this platform, PDX1 has been identified as a potential actionable gene for PDAC, therefore, RNAi therapy, gene therapy and small inhibitory drugs, all targeting PDX1, serve as potential targeted adjuvant therapies. Preclinical studies support the hypothesis that identification of PDAC actionable genes could permit translation of a patient's genomic information into precision targeted adjuvant therapy for PDAC.
胰腺导管腺癌（PDAC）是一种致命的癌症，由于早期诊断不佳和缺乏有效的治疗选择，其总体5年生存率低于5%。最有效的治疗方法仍然是手术，然而，有效的辅助治疗可以提高术后生存率。21世纪初，从组学技术中获得的关于PDAC的大量信息是一项了不起的成就。然而，从组学数据（包括下一代测序数据）中获得的信息尚未成功影响到PDAC患者的治疗。因此，我们提议开发一个可操作的基因组平台，将患者PDAC的临床可操作基因与潜在的靶向辅助治疗相匹配。利用这个平台，PDX1已被确定为PDAC的一个潜在可操作基因，因此，所有针对PDX1的RNA干扰疗法、基因疗法和小分子抑制药物都可作为潜在的靶向辅助治疗。临床前研究支持这样的假设，即识别PDAC的可操作基因可以将患者的基因组信息转化为针对PDAC的精准靶向辅助治疗。
