Abstract
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.
Highlights
Gastrointestinal cancers are a significant public health concern worldwide
Esophageal cancer has an incidence of 17,290 cases a year in the United States (USA), and patients who are inflicted typically experience a reduced quality of life [20]
Pancreatic cancer has an incidence of 55,440 cases per year and more than 21,000 deaths each year in the USA [20]
Summary
Gastrointestinal cancers are a significant public health concern worldwide. They have a considerable impact on health economics that permeates multiple aspects of healthcare ranging from screening and prevention to hospice care [1]. In the United States, colorectal cancer is the fourth leading cause of cancer mortality. Pancreatic cancer and hepatocellular cancer feature in the ten most lethal cancers in the United States [2]. Given the tremendous unmet therapeutic need for these cancers, novel approaches are in imminent need. Oncovirotherapy using adenoviruses (Ads) represents a very attractive anti-cancer therapeutic platform. This review will focus on the evolution of adenoviral bioengineering and manipulation in esophageal, gastric, pancreatic, liver, biliary, and colorectal cancers. The cell biology of a vast heterogeneity of tumors in each organ is beyond the scope of this review
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