Recent review highlights need to gain a broader scientific view of cancer to better prevent and treat it.
From: University of Alberta
By Adrianna MacPherson
April 21, 2022 -- While cancer is a genetic disease,
the genetic component is just one piece of the puzzle — and researchers need to
consider environmental and metabolic factors as well, according to a research review by
a leading expert at the University of Alberta.
Nearly all the theories
about the causes of cancer that have emerged over the past several centuries
can be sorted into three larger groups, said David Wishart,
professor in the departments of biological
sciences and computing science.
The first is cancer as a genetic disease, focusing on the genome, or the set of
genetic instructions that you are born with. The second is cancer as an
environmental disease, focusing on the exposome, which includes everything your
body is exposed to throughout your life. The third is cancer as a metabolic
disease, focusing on the metabolome, all the chemical byproducts of the process
of metabolism.
The metabolic
perspective hasn’t had much research until now, but it’s gaining the interest
of more scientists, who are beginning to understand the metabolome’s role in
cancer.
The genome, exposome
and metabolome operate together in a feedback loop as cancer develops and
spreads.
According to the data,
heritable cancers account for just five to 10 per cent of all cancers, Wishart
said. The other 90 to 95 per cent are initiated by factors in the exposome,
which in turn trigger genetic mutations.
“That’s an important
thing to consider, because it says that cancer isn’t inevitable.”
The metabolome is
critical to the process, as those genetically mutated cancer cells are
sustained by the cancer-specific metabolome.
“Cancer is genetic, but
often the mutation itself isn’t enough,” said Wishart. As cancer develops and
spreads in the body, it creates its own environment and introduces certain
metabolites. “It becomes a self-fuelled disease. And that’s where cancer as a
metabolic disorder becomes really important.”
The multi-omics
perspective, in which the genome, exposome and metabolome are all considered in
unison when thinking about cancer, is showing promise for finding treatments
and for overcoming the limitations of looking at only one of these
factors.
For example, Wishart
explained, researchers who focus only on the genetic perspective are looking to
address particular mutations. The problem is, there are around 1,000 genes that
can become cancerous when mutated, and it typically takes at least two
different mutations within these cells for cancer to grow. That means there are
a million potential mutation pairs, and “it becomes hopeless” to narrow down
the possibilities when seeking new treatments.
But when considering
cancer from the metabolic perspective, there are just four major metabolic
types, said Wishart. Rather than trying to find a treatment plan for one
specific mutation combination amongst a million, determining the patient’s
cancer metabolic type can immediately guide doctors in deciding on the best
treatment for their specific cancer.
“It really doesn't make
a difference where the cancer is — it’s something you’ve got to get rid of.
It’s how it thrives or grows that matters,” said Wishart. “It becomes a
question of, ‘What’s the fuel that powers this engine?’”
Wishart cautioned that
health-care providers still need a mix of therapeutics for cancer, and noted
that a deeper understanding of the metabolome and its role in the cancer
feedback loop is also critical to preventing cancer.
“If we understand the
causes of cancer, then we can start highlighting the known causes, the
lifestyle issues that introduce or increase our risk,” he said.
“From the prevention
side, changing our metabolism through lifestyle adjustments will make a huge
difference in the incidence of cancer.”
The research review was
funded by Genome Canada,
the Canadian Institutes of
Health Research and the Canada
Foundation for Innovation.
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