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The role of genes in cancer
The revolution in the understanding of genetics is changing the way scientists
look at disease. And Dr. Ken Kao’s developmental biology lab is making
sure Memorial’s Faculty of Medicine is at the forefront of such an
understanding of cancer and certain congenital defects.
Dr.
Ken Kao
On Oct. 31, as part of the Health Research Awareness Month
celebrations, Dr. Kao gave a talk titled Beyond Proteomics: Developmental
Biology and Health Research. Developmental biology is the study of how
cells differentiate and replicate through the various stages of the development
of living organisms. Dr. Kao argued that such research is crucial if medical
science is to gather the full benefits of recent advances in genetic and
cellular biology. At conception, each of us is given a personalized set
of genetic instructions from our parents that help us survive through
our lives. “Health care research needs to understand what the survival
kits of the body are made of,” he said.
Blue
Lake
Much of this understanding hinges on how cells function
within the normally developed, healthy body. One of the key revelations
of Dr. Kao’s work, funded by the Canadian Institutes of Health Research
and the Cancer Research Society, is that cancer is the result of cells
crucial to the body’s development gone wrong. “Cancer results
when some cells cease to coexist in the body,” he pointed out. “Developmental
models provide explanations on how cells develop the ability to live together
in a community.
“It is long known that the cellular and genetic mechanisms governing
development between different species from flies to humans are well-conserved,”
Dr. Kao said. “Using species such as frogs will provide us the theoretical
directions to develop strategies for the treatment of cancer and congenital
defects in humans.”
An example of this is the work of one of Dr. Kao’s students, Blue
Lake. Lake is doing a PhD with financial support from the Canadian Institute
for Health Research, studying the developmental patterns of the frog (XXenopus)
when a specific gene (XREL 3) is tinkered with. “What I am looking
at is the role of oncogenes, cancer causing genes, in normal development,
and more specifically in neural patterning in vertebrates,” Mr. Lake
told the Gazette. “We want to find what this gene normally does in
the embryo.” What they have found is that the normal expression of
this gene is crucial to the formation of the nervous system and the head.
“So far what I have shown is that if you basically knock out the
gene’s function, then you can have the loss of the head,” Mr.
Lake said. And this highlights the problem medical scientists face in
trying to solve the mystery of a cure for cancer: it originates in cells
that are needed for the normal functioning of the body. “At the moment
we are starting to believe that the reason it causes the tumours is the
same as why it gives rise to neural patterning.”
The body, according to Mr. Lake’s findings, is wedded to this gene,
clearly in sickness, but necessarily in health too. This is the irony:
if the gene over-expresses, the subject ends up with potentially cancerous
tumours; should it under-express, the body may not develop normally –
the brain and nervous system are dependent on its properly functioning
presence. “There are a lot of different genes that very finely control
different parts of the brain,” Mr. Lake explained. “They are
involved in the formation of a mass of cells that would give rise to that
structure. So if the gene is involved in controlling that kind of cell
growth, then you could see that if it mis-expressed in the skin, it would
promote cell growth, and thus it could give rise to a tumour.”
Dr. Kao’s presentation reiterated this point: he pointed out that
the normally developed body needs oncogenes such as those studied by Mr.
Lake, but that their “inappropriate expression” can lead to
cancer. His approach is to take a step back and get a better grip on the
basics of cellular development: “Our understanding of the mechanisms
of how this happens will help us understand these unfortunate cases of
congenital problems and cancer.”
From this, Dr. Kao believes medical researchers attempting to set up therapeutical
strategies for cancer will have a better chance of success. In particular,
it may allow them to steer clear of the controversy-fraught issue of stem
cells and genetic manipulation of embryos. “It is a dangerous route
to follow,” he commented on such strategies. “There are other
avenues to take. (The use of) stem cells is a very powerful technology
- if we don’t know enough about it, it can cause irreparable damage.”
