SYDNEY Australian researchers have discovered that a drug used for almost four decades to control parasitic infections can help inhibit the growth and spread of melanoma in mice.
Melanoma, the most serious type of skin cancer, develops in the cells (melanocytes) that produce melaninthe pigment that gives your skin its colour.
The drug, which is available over-the-counter in Europe, is a so-called anthelmintic used to control parasitic infections.
Researchers at the Sydney-based University of New South Wales (UNSW) found that the drug, flubendazole, inhibited growth and metastasis of human tumours grown in mice.
The finding was a result of a three-year collaboration between UNSW and the US scientists.
“We were surprised to discover that flubendazole’s anti-tumour effects involve its inhibition of a cell surface protein called programmed cell death protein-1 or PD-1,” lead author of the study Levon Khachigian said.
“When PD-1 is bound to another protein called PD-L1, it helps stop the immune system from killing cancer cells. PD-1 suppression releases the brakes on the immune system and allows immune cells to find and destroy tumours,” Khachigian said.
These studies associate flubendazole with PD-1 in an experimental system,” he said.
Treatment for melanoma has changed dramatically in recent years, with improvements in immunotherapy and the introduction of PD-1 inhibitors.
However, currently all clinically available PD-1 inhibitors are antibodies, requiring patients to
Unfortunately, significant challenges remain: many patients do not respond to existing PD-1 inhibitors or the response is not sustained.
No small molecule alternatives to antibody-based checkpoint inhibitors are clinically available, although a number are under development and one is currently being assessed in clinical trials.
The research has found that in mice, flubendazole is a novel small molecule inhibitor of PD-1.
“Patients on small molecule PD-1 inhibitors could potentially be dosed as outpatients. This would mean greater convenience, avoidance of intravenous administration and cost savings for chemotherapy units,” Khachigian said.
“Whilst flubendazole is an old drug, its use as a treatment for melanoma has not yet been tested in human trials.
“There is no regulatory approval for use of flubendazole for cancer patients, and thus it is not available for this indication. Patients should continue seeking the advice of their health professional,” he said.
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