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Oncolytic virotherapy: the questions and the promise

Authors Aurelian L

Received 18 January 2013

Accepted for publication 21 March 2013

Published 4 June 2013 Volume 2013:2 Pages 19—29


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Laure Aurelian

Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA

Abstract: Oncolytic virotherapy is a new strategy to reduce tumor burden through selective virus replication in rapidly proliferating cells. Oncolytic viruses are members of at least ten virus families, each with its advantages and disadvantages. Here, I briefly review the recent advances and key challenges, as exemplified by the best-studied platforms. Recent advances include preclinical proof of feasibility, clinical evidence of tolerability and effectiveness, and the development of new strategies to improve efficacy. These include engineered tumor selectivity and expression of antitumorigenic genes that could function independently of virus replication, identification of combinatorial therapies that accelerate intratumoral virus propagation, and modification of immune responses and vascular delivery for treatment of metastatic disease. Key challenges are to select “winners” from the distinct oncolytic platforms that can stimulate anti-cancer immunity without affecting virus replication and can lyse cancer stem cells, which are most likely responsible for tumor maintenance, aggressiveness, and recurrence. Preventing the emergence of resistant tumor cells during virotherapy through the activation of multiple death pathways, the development of a better understanding of the mechanisms of cancer stem-cell lysis, and the development of more meaningful preclinical animal models are additional challenges for the next-generation of engineered viruses.

Keywords: tumor cell lysis, virus replication, tumor selectivity, programmed cell death, immune response

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