Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham AL, 35294 USA.
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham AL, 35294 USA.
Pharmacol Res. 2020 May;155:104740. doi: 10.1016/j.phrs.2020.104740. Epub 2020 Mar 2.
Pancreatic cancer is a fatal disease. The five-year survival for patients with all stages of this tumor type is less than 10%, with a majority of patients dying from drug resistant, metastatic disease. Gemcitabine has been a standard of care for the treatment of pancreatic cancer for over 20 years, but as a single agent gemcitabine is not curative. Since the only therapeutic option for the over 80 percent of pancreatic cancer patients ineligible for surgical resection is chemotherapy with or without radiation, the last few decades have seen a significant effort to develop effective therapy for this disease. This review addresses preclinical and clinical efforts to identify agents that target molecular characteristics common to pancreatic tumors and to develop mechanism-based combination approaches to therapy. Some of the most promising combinations include agents that inhibit transcription dependent on BET proteins (BET bromodomain inhibitors) or that inhibit DNA repair mediated by PARP (PARP inhibitors).
胰腺癌是一种致命的疾病。所有阶段的这种肿瘤类型的患者五年生存率都低于 10%，大多数患者死于耐药性、转移性疾病。吉西他滨是治疗胰腺癌的标准药物已经超过 20 年，但作为单一药物，吉西他滨不能治愈。由于超过 80%不符合手术切除条件的胰腺癌患者的唯一治疗选择是化疗加或不加放疗，因此过去几十年一直在努力为这种疾病开发有效的治疗方法。本综述介绍了为确定针对胰腺肿瘤常见分子特征的药物以及开发基于机制的联合治疗方法而进行的临床前和临床研究。一些最有前途的组合包括抑制依赖 BET 蛋白的转录的药物（BET 溴结构域抑制剂）或抑制 PARP 介导的 DNA 修复的药物（PARP 抑制剂）。
