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 more efficiently.”

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 treated today.

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,” she said.

“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 one another.

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.