Faculty Articles

The intersection between viral oncolysis, drug resistance, and autophagy.

Publication Title

Biological chemistry

Publisher

Walter de Gruyter GmbH

ISSN

1431-6730

Publication Date

12-1-2015

Keywords

Autophagy, Drug Resistance, Humans, Neoplasms, Oncolytic Viruses, T-Lymphocytes

Abstract

Resistance to both cytotoxic and targeted therapies is a major problem facing cancer treatment. The mechanisms of resistance to unrelated drugs share many common features, including up-regulation of detoxifying pathways, activation of pro-survival mechanisms, and ineffective induction of cell death. Oncolytic viruses (OVs) are promising biotherapeutics for cancer treatment that specifically replicate in and lyse cancer cells. In addition to direct viral lysis, the anti-tumor effects of OVs are mediated via innate and adaptive immune responses, and several adaptation mechanisms such as autophagy appear to contribute to their anti-tumor properties. Autophagy is a versatile pathway that plays a key role in cancer survival during stressful conditions such as starvation or cytotoxic drug challenges. Autophagy also plays a role in mediating innate and adaptive immune responses by contributing to antigen presentation and cytokine secretion. This role of autophagy in regulation of immune responses can be utilized to design therapeutic combinations using approaches that either stimulate or block autophagy to potentiate therapeutic efficacy of OVs. Additional studies are needed to determine optimal multimodal combination approaches that will facilitate future successful clinical implementation of OV-based therapies.

DOI

10.1515/hsz-2015-0147

Volume

396

Issue

12

First Page

1269

Last Page

1280

Disciplines

Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy

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