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.
Highlights
Tumour progression is generally considered a stochastic process, but is associated with a series of hallmark changes that include, among others, resistance to apoptosis, metabolic deregulation, immune escape, growth independence, and enhanced angiogenic capacity [1] (Figure 1)
We highlight the similarities between the requirements for optimal cancer cell growth and successful viral replication, and the mounting evidence that tumours with altered metabolic and signaling networks provide a unique niche for oncolytic viruses (OVs) propagation
Poliovirus binds the cell surface receptor, nectin-like molecule 5 (NECL-5) [3], which is expressed at very low levels in normal tissues, but is broadly overexpressed in several solid tumours and in the proliferating vasculature that supports them, including glioblastoma multiforme and ovarian, prostate, colorectal, and lung carcinomas [4,5,6,7,8]
Summary
Tumour progression is generally considered a stochastic process, but is associated with a series of hallmark changes that include, among others, resistance to apoptosis, metabolic deregulation, immune escape, growth independence, and enhanced angiogenic capacity [1] (Figure 1). While some viruses are inherently oncophilic, it is possible to direct selective growth in cancer cells by inactivating or deleting certain viral virulence genes whose lost functions are complemented by mechanisms that drive malignancies and distinguish tumours from normal healthy tissues.
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