From Scourge to Cure: Tumour-Selective Viral Pathogenesis as a New Strategy against Cancer

PLoS Pathogens

Carolina S. Ilkow¹  John C. Bell¹  Jean-Simon Diallo²  Stephanie L. Swift³ 

[1] Centre for Innovative Cancer Therapeutics, Ottawa Health Research Institute, Ottawa, Ontario, Canada;Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada;Swift Science Writing, Hamilton, Ontario, Canada

关键词: Viral replication;    Oncolytic viruses;    Apoptosis;    Interferons;    Vesicular stomatitis virus;    Vaccinia virus;    Cell metabolism;    Drug metabolism;   

DOI  :  10.1371/journal.ppat.1003836

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Tumour mutations corrupt cellular pathways, and accumulate to disrupt, dysregulate, and ultimately avoid mechanisms of cellular control. Yet the very changes that tumour cells undergo to secure their own growth success also render them susceptible to viral infection. Enhanced availability of surface receptors, disruption of antiviral sensing, elevated metabolic activity, disengagement of cell cycle controls, hyperactivation of mitogenic pathways, and apoptotic avoidance all render the malignant cell environment highly supportive to viral replication. The therapeutic use of oncolytic viruses (OVs) with a natural tropism for infecting and subsequently lysing tumour cells is a rapidly progressing area of cancer research. While many OVs exhibit an inherent degree of tropism for transformed cells, this can be further promoted through pharmacological interventions and/or the introduction of viral mutations that generate recombinant oncolytic viruses adapted to successfully replicate only in a malignant cellular environment. Such adaptations that augment OV tumour selectivity are already improving the therapeutic outlook for cancer, and there remains tremendous untapped potential for further innovation.

【 授权许可】

CC BY