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Peter Mac researchers find key to melanoma resistance

Eliminating a key protein can vastly improve the effectiveness of melanoma treatment, researchers from Peter MacCallum Cancer Centre have found.

They say a protein called JUN causes resistance to treatment.

Four in 10 Australians with melanoma have a sub-type called BRAF-mutant, characterised by an overactive protein called BRAF.

Research over the past decade, including work at Melbourne-based Peter Mac, has led to therapies that inhibit BRAF.

Head of the Cancer Development and Treatment Laboratory at Peter Mac Mark Shackleton says anti-BRAF drugs are “wonderfully effective” and safe in most patients.

“Unfortunately, their benefit is only temporary and most patients develop resistance and the tumours return. Discovering how this resistance develops potentially allows us to fight back.”

Lead researcher Petranel Ferrao says the latest findings shed light on how melanomas become resistant to BRAF-targeted drugs.

“Our research found that tumour cells able to survive anti-BRAF treatment have higher levels of a protein called JUN, which acts to switch melanoma cells to a resistant state associated with spread of disease,” Dr Ferrao said.

By combining inhibitors to reduce JUN protein activity, researchers have been able to prevent this switch and eradicate most residual surviving melanoma cells “within a few days”.

The research was supported by grants from the Peter MacCallum Cancer Foundation, the CASS Foundation and the National Health and Medical Research Council.

The findings are published in US journal Science Signalling.

Australia has the highest incidence of melanoma in the world. Each year there are about 13,000 diagnoses and 1300 people die.

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