A study by NCCS found that gastric cancer patients with low levels of a protein, DOK6, survive four times longer than those with high levels.
Gastric cancer patients with low levels
of a particular protein, DOK6,
survive four times longer than
those with a lot of it, a study by scientists
at the National Cancer Centre Singapore (NCCS) has found.
The study is the first to link cancer
progression to this protein, which
was previously associated only with
brain development. It found that
many more signalling pathways
were activated in the gastric cancers
that had high amounts of DOK6.
Cancer cells depend on receiving
signals to grow, explained Professor
Kon Oi Lian, who led the study.
“What we think is happening is
when you have a lot of DOK6 in a cancer
cell, you are providing that cancer
cell with a lot of opportunities
for the signalling proteins to come together,
said Prof Kon, who is principal
investigator mentor at NCCS.
“They (DOK6 proteins) form a
molecular platform on which the
signalling proteins can assemble
themselves so that they can signal
The study looked at data from the
Cancer Genome Atlas, 17 gastric cancer
cell lines, and the primary gastric
cancers of 99 patients from the
Singapore General Hospital over
five years. The Cancer Genome Atlas
is a collaboration between the
United States National Cancer Institute
(NCI) and the National Human
Genome Research Institute.
Patients with low amounts of
DOK6 survived close to six years, or
2,100 days, while those with high
amounts of DOK6 survived close to
1 1/2 years (533 days).
The study also found that patients
with lower levels of DOK6
had something in common: a
“breakpoint” in chromosome 18, located
in FRA18C – a fragile site – in
the middle of the DOK6 gene.
The human genome has about 90
such fragile sites, which are specific
parts of chromosomes that tend to
break when cells are exposed to stress. Out of the 99 gastric cancer
patients studied, 22 per cent had a
breakage in FRA18C. Some fragile
sites are closely associated with the
development of cancer.
This is also the first study to link
that particular fragile site to cancer.
On how the discoveries can aid in
the fight against gastric cancer,
Prof Kon said if the signalling pathways
that become hyperactive
when DOK6 levels are elevated can
be identified, drugs can be used to
block them to suppress cancer.
The work was published in the
prestigious nature research journal
Precision Oncology in May.
Commenting on the research, Professor
Jimmy So, head and senior
consultant at the Division of Surgical
Oncology at the National University
Cancer Institute, Singapore,
said that while it was interesting, it
was still too early to see if it was relevant
to gastric cancer patients.
“The role of this gene is still unknown.
If it is drug-targetable, it
will be more interesting,” he said.
Prof Kon said the fact that there
are multiple signalling pathways
that fuel gastric cancer also warrants
a rethink of how cancers are
Targeted cancer therapies often
home in on a specific pathway
thought to promote tumour growth.
“If you silence one pathway, the
other pathways are still unaffected.
And I think that may be why these
targeted therapies, where you go
one at a time, don’t work very well,”
“Instead, blocking more than one
pathway at the same time, or very
close in time, might be a more effective
way to prolong survival and
even cure cancer.”
That could be through the use of
drugs that hit multiple pathways or
through using multiple drugs alongside
Prof Kon said she hopes to see
other research groups confirm the
results and find out if DOK6 is also
relevant in other common cancers
such as lung cancer.