Abstract
Naturally occurring oncolytic viruses are live, replicationproficient
viruses that specifically infect human cancer cells
while sparing normal cell counterparts. Since the eradication
of smallpox in the 1970s with the aid of vaccinia viruses,
the vaccinia viruses and other genera of poxviruses have
shown various degrees of safety and efficacy in pre-clinical
or clinical application for human anti-cancer therapeutics.
Furthermore, we have recently discovered that cellular tumor
suppressor genes are important in determining poxviral
oncolytic tropism. Since carcinogenesis is a multi-step
process involving accumulation of both oncogene and tumor
suppressor gene abnormalities, it is interesting that poxvirus
can exploit abnormal cellular tumor suppressor signaling
for its oncolytic specificity and efficacy. Many tumor suppressor
genes such as p53, ATM, and RB are known to play
important roles in genomic fidelity/maintenance. Thus, tumor
suppressor gene abnormality could affect host genomic
integrity and likely disrupt intact antiviral networks due to
accumulation of genetic defects, which would in turn result
in oncolytic virus susceptibility. This review outlines the characteristics
of oncolytic poxvirus strains, including vaccinia,
myxoma, and squirrelpox virus, recent progress in elucidating
the molecular connection between oncogene/tumor
suppressor gene abnormalities and poxviral oncolytic tropism,
and the associated preclinical/clinical implications. I would
also like to propose future directions in the utility of poxviruses
for oncolytic virotherapy.
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