Yokoda Raquel T, Nagalo Bolni M, Borad Mitesh J
Department of Medicine, Division of Hematology Oncology, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ 85205, USA.
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Biomedicines. 2018 Mar 11;6(1):33. doi: 10.3390/biomedicines6010033.
Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers.
胃肠道恶性肿瘤是具有挑战性的癌症,对全球医疗保健系统产生了巨大的经济和社会影响。虽然手术方法的进步使一部分患者受益,但晚期疾病患者的治疗仅取得了适度改善,这些患者的生存率提高有限。溶瘤腺病毒正在被开发用于治疗胃肠道恶性肿瘤。每个平台都在不断发展,以最大限度地提高肿瘤细胞杀伤效力,同时将毒性降至最低。使用嵌合启动子、前药转化酶、致死基因、肿瘤抑制基因和假型衣壳的肿瘤特异性生物工程腺病毒可为溶瘤病毒疗法的最终成功提供创新。本文将在特定胃肠道癌症的背景下回顾腺病毒平台的发展。从实验室研究到临床试验的实施,本综述旨在突出该领域从早期到当前状况的进展,因为它涉及腺病毒溶瘤疗法在胃肠道癌症中的应用。