Abstract
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy.
Highlights
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies
The anti-cancer activities from oncolytic viruses are a result from the direct lysis of cancer cells by the virus, and by cytotoxicity to cancer and stromal cells by activated innate and tumor specific immune cells [3,4]
In early preclinical studies conducted in hepatocellular carcinoma and colorectal tumor xenografts in mice models, IFN-inducing Vesicular Stomatitis Virus (VSV) have shown significant oncolytic activity with extensive tumor necrosis and prolongation of survival [49,50]
Summary
Viral therapies represent one of many potential immunotherapeutic strategies in the treatment of gastrointestinal cancers. Historical evidence has shown tumor regression or remission of several advanced malignancies after the inoculation of naturally occurring viruses, including chicken pox, measles or hepatitis viral infections [1]. These early observations led to the preclinical investigation for viral therapies as a treatment for cancer. The ability of oncolytic viral therapy to induce tumor cell apoptosis and stimulate an anti-tumor immune response has resulted in its interest as a potential treatment across various tumor types, including in the treatment of gastrointestinal malignancies, and will be reviewed in detail below (Table 1). PFS—progression free survival; OS—overall survival; SD—stable disease; PR—partial response; IV—intravenous; trmt—treatment; Ca—cancer; N/A—not applicable; Ref—references; IT—intratumorally; pts—patients. *—In months; NCT—National Clinical Trial
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