Division of Basic and Translational Medicine, Department of Surgery, University of Minnesota, MN, United States.
Curr Cancer Drug Targets. 2018;18(2):153-161. doi: 10.2174/1568009617666170222123925.
Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for the treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer. Our ultimate goal is to develop an oncolytic adenovirus enabling the treatment of patients with advanced or spread diseases by systemic injection. Systemic application of oncolytic therapy mandates more efficient and selective gene delivery and needs to embody sufficient antitumor effect even with limited initial delivery to the tumor location. In this review, the current status of oncolytic adenoviruses from the viewpoints of vector design and potential strategies to overcome current obstacles for its clinical application will be described. We will also discuss the efforts to improve the antitumor activity of oncolytic adenovirus, in in vivo animal models, and the combination therapy of oncolytic adenovirus with radiation and chemotherapy.
胰腺癌是一种侵袭性恶性疾病，尽管最近取得了一些进展，但目前对不可切除疾病的治疗效果相当有限。基因治疗/病毒疗法策略可能为包括胰腺癌在内的各种癌症的治疗提供新的选择。溶瘤腺病毒通过在肿瘤内扩增和对多种癌症的强烈细胞毒性作用显示出抗肿瘤作用，它已被用于开发用于胰腺癌的有效的溶瘤病毒治疗剂。我们的最终目标是开发一种溶瘤腺病毒，通过系统注射治疗晚期或扩散疾病的患者。溶瘤治疗的系统应用需要更有效的和选择性的基因传递，并需要体现足够的抗肿瘤作用，即使初始向肿瘤部位的传递有限。在这篇综述中，将从载体设计的角度描述溶瘤腺病毒的现状和克服其临床应用当前障碍的潜在策略。我们还将讨论提高溶瘤腺病毒在体内动物模型中的抗肿瘤活性以及溶瘤腺病毒与放疗和化疗联合治疗的努力。
