Shrinking melanomas by restoring a lost protein

University of Newcastle 2013–2015

In a discovery that made international headlines, Professor Xu Dong Zhang found the loss of a certain protein could cause melanoma to spread. When the team restored this protein back to normal levels, melanoma growth was stopped and some tumours even shrank in size, providing a landmark breakthrough for melanoma research.

Background

Melanoma is a major health problem in Australia. It is one of the most common cancers in men and women, and has a particularly heavy impact on young people. Despite this, there is currently no cure for melanoma once it has spread. Melanoma development is driven by a network within cancer cells, which sends out signals to promote growth. A key component of this network is a pathway called PI3K/Akt, which becomes abnormally activated in most melanomas. To date, the factors causing this activation have not been clarified and this has prevented treatments being created that target this pathway.

The research

Using a combination of molecular biology and biochemistry techniques, Professor Zhang and his team discovered that a protein called PIB5PA normally keeps the PI3K/Akt pathway under control.
When the protein is reduced or lost altogether, the pathway is activated and melanoma growth is stimulated. The team found that the loss of the PIB5PA protein is triggered by a biological chain reaction called ‘histone hypoacetylation’.
By blocking this reaction, the researchers showed that levels of PIB5PA could be bumped up and restored back to normal. By increasing the expression of this protein, melanoma growth was dramatically stopped. In some cases, the melanoma even shrank in size.

The impact

Currently it is difficult to treat melanoma once it has spread – except by cutting the cancer out. Over the past three years, the results of this research have captured worldwide attention and provided a much needed breakthrough in treating melanoma.

Professor Zhang has demonstrated that a lack of a certain molecule in a person’s body, as opposed to genetic mutations, could be a major cause of melanoma spreading. Professor Zhang’s project has taken the research community one step closer to designing personalised, molecular therapies for patients, and has highlighted a whole new way of stopping aggressive melanomas in their tracks.

The results have fundamentally changed the way we see melanoma, and now there is an opportunity to target the underlying biology of other cancer types in a similar way.