Oncolytic virotherapy for pancreatic cancer

Abstract

Within the past decade, many oncolytic viruses (OVs) have been studied as potential treatments for pancreatic cancer and some of these are currently under clinical trials. The applicability of certain OVs, such as adenoviruses, herpesviruses and reoviruses, for the treatment of pancreatic cancer has been intensively studied for several years, whereas the applicability of other more recently investigated OVs, such as poxviruses and parvoviruses, is only starting to be determined. At the same time, studies have identified key characteristics of pancreatic cancer biology that provide a better understanding of the important factors or pathways involved in this disease. This review aims to summarise the different replication-competent OVs proposed as therapeutics for pancreatic cancer. It also focuses on the unique biology of these viruses that makes them exciting candidate virotherapies for pancreatic cancer and discusses how they could be genetically manipulated or combined with other drugs to improve their efficacy based on what is currently known about the molecular biology of pancreatic cancer.

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

“…Semiconfluent monolayers of cells seeded in 24-well plates were infected at an MOI of 1, and after 1 h of absorption, inoculum was removed and replaced with 1 ml of serum-free medium. Gemcitabine (2 mM) and cisplatin (0.8 M) (GemϩCisp), two common chemotherapeutic agents used for PDA treatment (7,41), were included in combination as a positive control. FBS was added to each well, for a final concentration of 10%, approximately 1 h postcollection to ensure cell membrane integrity for the labeling process.…”

“…A number of oncolytic viruses have been tested for efficacy against pancreatic cancer, including adenoviruses, herpesviruses, parvoviruses, reoviruses, and poxviruses. Some of these viruses, when they show particular preferences for a specific mutation along a signaling pathway, show selectivity for cancer cells based on these aberrant pathways (2,7). While some have demonstrated appreciable efficacy in preclinical models, the great genetic diversity of PDAs encountered in the clinical setting often leads to unsatisfactory results in clinical trials and reaffirms the need to investigate additional viral classes that offer alternative modes of tumor-specific targeting (7).…”

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

“…However, so far PDA cells have displayed mixed susceptibility to OVs (Lee et al, 2014;Moerdyk-Schauwecker et al, 2012;Murphy et al, 2012;Wennier et al, 2011), underscoring that virotherapy for tumours which tend to be heterogeneous in nature should not rely on a short list of possible candidates.…”

Complementary Induction of Immunogenic Cell Death by Oncolytic Parvovirus H-1PV and Gemcitabine in Pancreatic Cancer

“…Novel therapies employing oncolytic viruses have emerged as promising anticancer modalities (22). The autonomous parvoviruses H-1PV and prototype strain of the minute virus of mice MVMp are rarely virulent in their natural adult hosts but possess the ability to infect, propagate in, and kill transformed cells (23)(24)(25).…”