Scientists seek new ways to kill deadly skin cancers

University of Auckland scientists are striving to bring down New Zealand's melanoma death rate, which is the highest in the world.

The Winn Trust has granted $1 million for research into melanoma led by Associate Professor of Pharmacology Stephen Jamieson and Dr Dean Singleton from the University’s Auckland Cancer Society Research Centre and Centre for Cancer Research.

Every year, more than 7,000 melanomas are diagnosed and approximately 300 people die from the skin cancer in New Zealand.

Jamieson is using cutting-edge gene-editing technologies to try to develop new treatments to tackle melanomas caused by a mutation of the NRAS gene. This mutation is found in about 15 to 20 percent of melanomas, but there is no specific treatment at present.

“Melanoma is a major issue in New Zealand – with Australia, we have the highest incidence and mortality rates in the world.

“Immunotherapy can be used to treat melanomas, but if that fails, there are no effective treatment options for NRAS-mutant melanomas and there’s a very poor prognosis – so there’s an urgent need for new treatments,” he says.

Under Jamieson’s supervision, former PhD student Andrea Gu investigated weaknesses in melanoma’s genetic makeup, before making a groundbreaking discovery – that the SHOC2 gene is essential for the growth of melanoma cells with the NRAS mutation.

This research, funded by Cancer Society New Zealand and Cancer Research Trust New Zealand, was published in the journal, Cancer Communications, last year.

Gu won a John Gavin Postdoctoral Fellowship from Cancer Research Trust New Zealand and Melanoma New Zealand to research at the Wellcome Sanger Institute at Cambridge University in the UK. She plans to return to Waipapa Taumata Rau, University of Auckland to share her knowledge.

With $200,000 from Cancer Society New Zealand, Jamieson’s research team plans to investigate billions of compounds to see if they can block the SHOC2 protein and kill melanoma cells with NRAS mutations.

Promising compounds will be tested, with the goal of developing a new drug or combination of drugs to treat this type of melanoma.

Jamieson hopes a new treatment will be ready to test in patients in just over five years.

Singleton’s research is focused on hunting down the reasons that immunology treatments are not helping about 60 percent of patients with metastatic melanomas – those which have spread from the skin to other parts of the body, such as the lungs, brain or liver.

Melanoma cells are complex and can take many forms, some of which are not recognised by new treatments that use the body’s immune cells to fight cancer, says Singleton, who is a senior lecturer in molecular medicine and pathology.

Singleton hopes discovering how some melanoma cells dodge existing treatments and finding their vulnerabilities might pave the way to developing new treatments with higher success rates.

“Immunology treatments aim to kill melanoma cells, but sometimes they make the cells change. Then cancer cells can hide from the treatment and are less able to be recognised and killed.

“We’re investigating what’s going on in those different melanoma cell differentiation states and how best to target them,” he says.

Cancer Society Auckland Northland has funded research supervised by Singleton and led by PhD student Claire Palma that is investigating the PHD2 gene and oxygen-sensing pathways in melanoma cells. This gene seems like a weak point that drugs could potentially alter to wipe out some melanomas.

“It’s exciting to be involved in this project, which is trying to make new medicines that will block PHD2 and will hopefully work better at killing melanoma cells,” Singleton says.

Both Jamieson and Singleton say a valuable resource powering their search for cures for melanoma is the New Zealand Melanoma living biobank.

It holds more than 100 cell lines grown in the lab from samples donated by New Zealand melanoma patients.

“We’re lucky to have this cell collection, which includes all the types of melanoma we see in our population, so we’re well positioned to try to find new drug treatments,” says Jamieson.