The inhibitor HET0016 blocks production of the chemical 20-HETE, or 20-Hydroxyeicosatetraenoic acid, which normally functions as a regulator of blood pressure and blood flow. But is also used by tumour cells to give a siren call that beckons the bone marrow to send whatever the tumours need to survive.
A new treatment being developed by scientists has successfully inhibited the production of a chemical that controls the growth and spread of human glioblastomas and breast cancer — the two most aggressive forms of cancers found in humans today.
Tested in laboratory models, researchers at Medical College of Georgia Augusta University used an inhibitor, called HET0016, in combination with chemotherapy, to effectively control growth of tumour cells.
“Our idea is that the most aggressive tumours have the same basic mechanisms of growth and spread” — a siren call that beckons the bone marrow to send along whatever the tumours need to survive and thrive, says senior author of the study Ali S. Arbab, leader of the Tumor Angiogenesis Initiative at the Georgia Cancer Centre.
The inhibitor HET0016 blocks production of the chemical 20-HETE, or 20-Hydroxyeicosatetraenoic acid, which normally functions as a regulator of blood pressure and blood flow. It also helps the body fight infection and protect us from cancer and other invaders in normal conditions.
“But tumors express too much 20-HETE and the chemical turns on us, first by activating immune cells that will send the cytokines that become the siren call to our bone marrow,” says Dr BR Achyut, the corresponding author of the study.
“Once the bone marrow cells show up, 20-HETE also turns the cells’ usually lifesaving functions, like making blood vessels and populating our immune system, against us,” he adds.
This includes bolstering the primary tumour site and in the case of breast cancer, helping prepare remote sites in places like the brain, lung and liver.
To reduce the many ill effects of too much 20-HETE, the scientists used the inhibitor drug alternately with the chemotherapy drug temozolomide for three to six weeks on rats to test the effect of the treatment.
The study found that the 20-HETE blocker does not kill tumour cells, rather essentially puts them on hold. It was also found that chemotherapy does kill tumour cells but when the tumours start dying they actually increase their release of cytokines as another cry for survival, “which is another good reason to also directly target the call for assistance that tumours are sending,” says Arbab.
While a 20-HETE inhibitor has not yet been used in humans, commonly used drugs like aspirin and Celebrex, which target other arachidonic acid pathways, are widely used.
The scientists’ studies indicate that healthy bone marrow production is untouched by 20-HETE inhibition because it’s blocking the tumour’s signals not the bone marrow directly.
The study was recently published in the International Journal of Molecular Sciences.
