Molecular Pathways: Rodent Parvoviruses-Mechanisms of Oncolysis and Prospects for Clinical Cancer Treatment

• Published in: Clinical cancer research 2012-07, Vol.18 (13), p.3516-3523
• Main Authors: NÜESCH, Jurg P. F, LACROIX, Jeannine, MARCHINI, Antonio, ROMMELAERE, Jean
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Clinical Trials as Topic; Host-Pathogen Interactions; Humans; Medical sciences; Neoplasms - therapy; Oncolytic Virotherapy; Oncolytic Viruses - physiology; Parvovirus - physiology; Pharmacology. Drug treatments; Viral Tropism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-11-2325

Rodent parvoviruses (PV) are recognized for their intrinsic oncotropism and oncolytic activity, which contribute to their natural oncosuppressive effects. Although PV uptake occurs in most host cells, some of the subsequent steps leading to expression and amplification of the viral genome and production of progeny particles are upregulated in malignantly transformed cells. By usurping cellular processes such as DNA replication, DNA damage response, and gene expression, and/or by interfering with cellular signaling cascades involved in cytoskeleton dynamics, vesicular integrity, cell survival, and death, PVs can induce cytostasis and cytotoxicity. Although productive PV infections normally culminate in cytolysis, virus spread to neighboring cells and secondary rounds of infection, even abortive infection or the sole expression of the PV nonstructural protein NS1, is sufficient to cause significant tumor cell death, either directly or indirectly (through activation of host immune responses). This review highlights the molecular pathways involved in tumor cell targeting by PVs and in PV-induced cell death. It concludes with a discussion of the relevance of these pathways to the application of PVs in cancer therapy, linking basic knowledge of PV-host cell interactions to preclinical assessment of PV oncosuppression.