Researchers at the University of Alberta have discovered that stopping an …


Stopping an enzyme may help stop the spread of some tumours.

Researchers at the University of Alberta Faculty of Medicine and Dentistry Department of Biochmistry found the enzyme autotaxin is to blame for tumour growth, spread and resistance to treatment in breast and thyroid cancers.

Professor David Brindley says by cutting down on the autotaxin’s activity, growth in breast tumours can be cut by 70 per cent. It also helps stop the spread of tumours.

While the research is in the early stages, it has potential, he said.

“A third of women with breast cancer die from metastasis and many thyroid cancer patients do not respond well to treatment. If we can improve the treatment of these patients, it will be a very big deal.”

The autotaxin enzyme makes lysophosphatidate or LPA, which helps cancer cells survive, grow, move and invade. It also causes resistance to chemotherapy and radio therapy. The group found by inhibiting autotaxin, LPA was reduced.

“Autotaxin causes a lot of serious problems in the treatment of breast and other cancers. Essentially, the body hijacks this enzyme to help a tumour grow, survive treatment and spread to other areas of the body,” said Brindley, senior author of a series of related studies.

“By inhibiting it, we found we could block the growth of breast and thyroid tumours and break the cycle of treatment resistance.”

Autotaxin is normally involved in wound repair and tissue regeneration. It also drives inflammatory conditions such as colitis, arthritis and cancer. Brindley believes it is this inflammation-associated event that is especially problematic and could fuel breast and thyroid tumour growth.

Brindley’s team included co-authors Matthew Benesch, a Vanier Scholar, Killam Laureate, and MD/PhD candidate in the Faculty of Medicine Dentistry; Ganesh Venkatraman, an Alberta Innovates-Health Solutions sponsored PhD candidate; Xiaoyun Tang, a Canadian Breast Cancer Foundation-funded postdoctoral fellow; and endocrine surgeon Todd McMullen. They used a drug developed by Ono Pharmaceuticals in Japan to inhibit autotaxin activity.

Daily doses of the drug reduced the initial phase of breast tumour growth by 60 to 70 per cent in experimental models. The inhibitor compound also cut tumour metastasis to the lungs by a similar margin. Later tests with a different technique for blocking the effects of lysophosphatidic acid enabled the team to block breast and thyroid tumour growth and spread by up to 80 per cent.

Brindley said his team was surprised when Benesch discovered that autotaxin is not produced by breast cancer cells themselves, but largely by the surrounding breast fat tissue. As the tumour develops and causes inflammation in the breast, the fat tissue produces more autotaxin, aggravating the problem by making the tumour grow more, metastasize and resist further treatment.

“With this drug we are cutting this vicious cycle,” he said, explaining that by blocking autotaxin the researchers saw a five-fold reduction in inflammation markers in the blood, and a 10-fold reduction in the breast fat tissue adjacent to the tumour.

The research team is now trying to promote the testing of the compound in human clinical trials in Edmonton — the first autotaxin inhibitor to make it to the clinic after more than 10 years of research.

The research is funded by the Canadian Breast Cancer Foundation, Alberta Cancer Foundation, Canadian Institutes of Health Research and Alberta Innovates — Health Solutions.



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