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

Abstract

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.

Inactivated Sendai Virus Strain Tianjin Induces Apoptosis in Human Breast Cancer MDA-MB-231 Cells

“…A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, measles virus, herpes simplex virus, vesicular stomatitis virus, Newcastle disease virus, and reovirus (Russell et al, 2012;He et al, 2014;Ilkow et al, 2014;Schenk et al, 2014 (Kaneda, 2003;Ito et al, 2005;Kaneda et al, 2005;Zhang et al, 2008). In addition, HVJ-E has been extensively used in anticancer vaccination strategies (Hiraoka et al, 2004;Yamano et al, 2006).…”

Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy

“…Various oncolytic viruses from diverse virus families have been developed and have advanced into clinical evaluation (1,2). Recently, a modified herpes simplex virus 1 (HSV-1) termed talimogene laherparepvec (Imlygic; Amgen) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent melanoma after initial surgery (3).…”

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

“…Derived from a variety of viral species, OVs are often engineered to exploit well-known hallmarks of cancer, including deregulated metabolism and proliferation, evasion of cell death and inefficient antiviral signalling 1 . Within the tumour, these agents destroy the malignancy by inducing direct oncolysis, stimulating antitumour immune responses and promoting tumour-vasculature shutdown (reviewed in ref.…”