The growth and metastasis of tumors suppresses the inhibitor of autotaxin

Scientists have broken the "vicious circle" of inflammation leading to the growth and metastasis of cancer

Nanonews Network based on materials from the University of Alberta (Stopping breast cancer's 'vicious cycle' – VM)

A group of scientists from the University of Alberta has developed a new approach to the fight against breast and thyroid cancer, in which an enzyme is used as a pharmacological target, which, according to researchers, is the culprit of the "vicious circle" of tumor growth, metastasis and resistance to treatment.

A group led by Professor of biochemistry David Brindley found that suppressing the activity of an enzyme known as autotaxin reduces the growth of primary breast tumors by up to 70 percent. In addition, blocking autotaxin prevents, to about the same extent, the spread of tumors to other organs, that is, their metastasis. Autotaxin is responsible for the synthesis of lysophosphatidyl acid (lysophosphatidic acid) in the body – a signaling molecule that stimulates the survival, growth and metastasis of cancer cells – and is also associated with the development of resistance to chemotherapy and radiation therapy.

"Autotaxin is the cause of many serious problems in the treatment of breast cancer and other types of cancer. In fact, the body uses this enzyme to help the tumor grow, resist treatment and spread to other organs," explains Professor Brindley. "By suppressing it, we were able to block the growth of tumors of the mammary and thyroid glands and broke the cycle of drug resistance."

Normally, autotaxin is involved in wound healing and tissue regeneration. But it also contributes to the development of inflammatory diseases such as colitis, arthritis and cancer. Professor Brindley believes that the main factor stimulating tumor growth in the mammary and thyroid glands here is precisely the effect of autotaxin, which is associated with inflammation.

According to Brindley, the tumor can be considered a non-healing wound. The body uses autotaxin to help the tumor grow, resist chemo and radiation therapy, and metastasize. During growth and when damaged by drugs, the tumor produces an increasing number of inflammatory mediators, which, in turn, leads to the production of even more autotaxin. As a consequence, it enhances the synthesis of inflammatory mediators. Researchers have found that by breaking this vicious circle with an autotaxin inhibitor, the growth of mammary and thyroid tumors can be blocked.

To suppress the activity of autotaxin, Professor Brindley and his colleagues used a drug developed by the Japanese firm Ono Pharmaceuticals (so far it is known as ONO-8430506).

In experimental models, daily administration of this drug suppressed the growth of primary breast tumors and their metastases to the lungs by 60-70 percent. In later tests, which used a different method of blocking the effects of lysophosphatidylic acid, the reduction in the growth of breast and thyroid tumors reached 80 percent.

Scientists were surprised to learn that autotaxin is produced not by the breast cancer cells themselves, but mainly by the fatty tissue surrounding the mammary gland. As the tumor grows and causes inflammation in the gland, adipose tissue produces more and more autotaxin, exacerbating the problem.

Now researchers are organizing the testing of this drug in a clinical setting. This is the first autotaxin inhibitor that has reached the clinic in ten years of research. According to Brindley, this suggests that all this is not a hypothetical "crane in the sky", but a potentially new treatment method that can be used in combination with chemotherapy.

"We have shown that this autotaxin inhibitor has great therapeutic potential, even if we take into account that we are at an early stage of research," says the scientist. "A third of women with breast cancer die from metastases, and many patients with thyroid cancer do not respond to treatment. If we can improve the treatment of these patients, we will do a great job."

"This discovery is very interesting from different points of view," Liz Viccars, president of one of the branches of the Canadian Breast Cancer Foundation, commented on the work of Professor Brindley. "This is a remarkable demonstration of fundamental scientific research potentially leading to the development and implementation of personalized drugs and cancer treatments. Such discoveries will improve the quality of life and care for patients with breast cancer and other types of cancer."

The study has been published in three journals: The Journal of Lipid Research, FEBS Letters and The FASEB Journal (Benesch et al., Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice).

Portal "Eternal youth" http://vechnayamolodost.ru08.12.2014