Ann. Méd. Vét., 2013, 157 (1), pp 5-14 Oncolytic virotherapy with myxoma virusKRYGIER D., GILLET L., MARLIER D.Abstract :
The myxoma virus
(MYXV) is a poxvirus that causes
myxomatosis in European rabbits
(Oryctolagus cuniculus). The
MYXV is non-pathogenic for the
others vertebrate species, including
the man. The MYXV has also
an unexpected tropism for human
cancer cells in vitro and an oncolytic
potential in vivo. The permissiveness
of these cells for the
MYXV is intimately linked to the
basal level of endogenous phosphorylated
Akt. This enzyme is
a serine/threonine protein kinase
that plays a key role in multiple
cellular processes and belongs
to the PI3k/Akt/mTOR signaling
pathway, which is amplified by
the oncogenesis. The viral ankyrin-
repeat protein, M T5, interacts
with Akt and modulates the tropism
of MYXV for human tumour
cells. A regulator of cell growth
and metabolism downstream of
Akt, mTOR, is specifically inhibited
by rapamycin. Thus, the use
of rapamycin in combination with
MYXV enhances the level of phosphorylated
Akt, and consequently,
increases its oncolytic capacity. A
better pharmacological control of
Akt signaling pathway or a genetic
modification of its genome is a
key step to create one of the new
treatments of human’s cancers. Get the PDF Contact person : dmarlier@ulg.ac.be |