A New Role for Vitamin D: The Enhancement of Oncolytic Viral Therapy in Pancreatic Cancer.

Christopher Larocca,Susanne Warner

doi:10.3390/biomedicines6040104

Christopher Larocca, Susanne Warner

Open Access

https://doi.org/10.3390/biomedicines6040104

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Journal: Biomedicines	Publication Date: Nov 5, 2018
Citations: 13	License type: CC BY 4.0

Affiliation: City Of Hope National Medical Center

Abstract

Oncolytic viruses have emerged as a novel class of anti-cancer therapeutics with one virus already receiving United States Food and Drug Administration (FDA) approval (talimogene laherparepvec) and many others undergoing testing in clinical trials. These viruses have direct lytic effects on tumor cells as well as immunomodulatory functions to increase inflammatory cell infiltrates in the tumor microenvironment. Despite all of the advances in cancer care, pancreatic cancer remains a highly lethal malignancy. One of the main barriers to successful systemic treatment of the disease is the fibrotic tumor stroma, as the unique extracellular matrix creates an environment that promotes tumor growth and is resistant to chemotherapy and other anti-cancer agents. The pleiotropic effects of Vitamin D have been widely studied, but recent research has now demonstrated it to be an effective agent in modulating pancreatic cancer stroma to facilitate the enhanced delivery of cytotoxic chemotherapy and immunogenicity in response to treatment. This review will explore the combination of Vitamin D with oncolytic viruses and how this novel application of Vitamin D’s ability to modulate pancreatic tumor stroma may result in a potential mechanism for increasing the efficacy of oncolytic virotherapy in pancreatic cancer.

Highlights

Oncolytic viruses are emerging therapeutics in the cancer treatment armamentarium
Oncolytic virotherapy is a valuable member of the cancer treatment armamentarium
vitamin D receptor (VDR)-stromal reprogramming weakens the capacity of the pancreas stellate cells (PSC) to support cancer growth via stromal remodeling, alters the PSC phenotype to a more quiescent nature, and reduces fibrotic content and increases tumor vasculature [11]

Summary

Introduction

Oncolytic viruses are emerging therapeutics in the cancer treatment armamentarium. Oncolytic viruses can be designed to selectively replicate in cancer cells through the use of a tumor-specific promoter or through key deletions in viral genomes [3,4,5]. Spurred on by the success of T-Vec, many other oncolytic viruses are entering into clinical trials as monotherapy agents or as part of a combination therapy regimen [2]. Oncolytic vectors have demonstrated synergy with chemotherapy and radiation, and many new studies have shown promising effects when these viruses are combined with immunotherapies [10,11]. This review will explore the nature of Vitamin D and its pleiotropic effects, with particular attention to treatment of pancreatic cancer, and will further explore the notion of enhanced oncolytic viral efficacy following Vitamin D treatment

The Basics of Vitamin D

Vitamin D and the Stroma of Pancreatic Cancer

A Phase II Pilot Trial of Paclitaxel Protein Bound Plus Cisplatin Plus

Vitamin D Use in Oncolytic Virotherapy

Findings

Conclusions