June 14, 2013 — Here's a good reason to pay
attention in math class. Today Nature
Communications has published a paper from
Ottawa researchers outlining how advanced
mathematical modelling can be used in the
fight against cancer. The technique predicts
how different treatments and genetic
modifications might allow cancer-killing,
oncolytic viruses to overcome the natural
defences that cancer cells use to stave off viral
infection.
"Oncolytic viruses are special in that they
specifically target cancer cells," explains Dr.
Bell, a senior scientist at the Ottawa Hospital
Research Institute and professor at the
University of Ottawa's Faculty of Medicine.
"Unfortunately, cancer is a very complicated
and diverse disease, and some viruses work
well in some circumstances and not well in
others. As a result, there has been a lot of
effort in trying to modify the viruses to make
them safe, so they don't target healthy tissue
and yet are more efficient in eliminating
cancer cells."
Dr. Bell and co-author Dr. Mads Kaern, an
assistant professor in the University of
Ottawa's Faculty of Medicine and Canada
Research Chair at the University's Ottawa
Institute of Systems Biology, led a team that
has used mathematical modelling to devise
strategies for making cancer cells exquisitely
sensitive to virus infection -- killing them
without affecting normal, healthy cells.
"By using these mathematical models to
predict how viral modifications would actually
impact cancer cells and normal cells, we are
able to accelerate the pace of research," says
Dr. Kaern, who is also cross-appointed to the
University's Department of Physics. "It allows
us to quickly identify the most promising
approaches to be tested in the lab, something
that is usually done through expensive and
time-consuming trial and error."
Drs. Bell and Kaern have established a
mathematical model that described an
infection cycle, including the way a virus
replicated, spread and activated cellular
defense mechanisms. From there, they used
knowledge about key physiological differences
between normal cells and cancer cells to
identify how modifying the genome of the
virus might counter the anti-viral defenses of
cancer cells. Model simulations were
remarkably accurate, with the identified viral
modifications efficiently eradicating cancer in
a mouse model of the disease.
"What is remarkable is how well we could
actually predict the experimental outcome
based on computational analysis," says Dr.
Bell. "This work creates a useful framework for
developing similar types of mathematical
models in the fight against cancer."
The research, funded by an innovation grant
from the Canadian Cancer Society, is only the
beginning, explains Dr. Kaern. "We worked
with a specific kind of cancer cell. We will now
expand that to look at other cancer cell types
and see to what degree the predictions we
made in one special case can be generalized to
others, and to identify strategies to target
other types of cancer cells."
The findings may also help researchers better
understand the interaction between these
cancer cells and the virus. While one magic
cure-all will likely never happen due to
cancer's complexity, the researchers have
developed a framework where they can learn
more about the disease in the cases where the
simulations don't match.
"From my perspective, that's the most
interesting part," concluded Dr. Kaern. "The
most fascinating thing is to challenge existing
knowledge represented in a mathematical
model and try to understand why these models
sometimes fail. It's a very exciting opportunity
to be a part of this, and I am glad that our
efforts in training students in computational
cell biology have resulted in such a significant
advancement."
Story Source:
The above story is reprinted from materials
provided by Ottawa Hospital Research
Institute .
Note: Materials may be edited for content and
length. For further information, please contact
the source cited above.
And [ Science daily ]
Journal Reference:
1. Fabrice Le Bœuf, Cory Batenchuk, Markus
Vähä-Koskela, Sophie Breton, Dominic Roy,
Chantal Lemay, Julie Cox, Hesham Abdelbary,
Theresa Falls, Girija Waghray, Harold Atkins,
David Stojdl, Jean-Simon Diallo, Mads Kærn,
John C. Bell. Model-based rational design of
an oncolytic virus with improved
therapeutic potential . Nature
Communications, 2013; 4 DOI: 10.1038/
ncomms2974
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