Hunter researchers on track to ‘kill melanoma cells’

Source: Newcastle Herald, March 2015

HUNTER researchers have exposed the double-life of a protein known as RIP1, which they hope will lead to the development of a new generation of targeted melanoma drugs.

The molecule, Receptor-Interacting Protein kinase 1, has previously been linked to naturally occurring cell death but little attention has been paid to its pro-survival function in melanoma cells.

Hunter Medical Research Institute cancer program deputy director Xu Dong Zhang believes the molecule sits near the top of the melanoma signal pathway. Controlling its levels could therefore curb a series of subsequent signals and prevent further tumour growth.

“We started investigating RIP1 from a perspective of necrotic cell death before finding that it actually plays an important role in regulating melanoma cell survival … we had to turn our entire thinking around,” Professor Zhang said.

“It appears to be upregulated from the earliest stages of melanoma so if we can inhibit the molecule’s survival mechanism we believe we’ll be able to kill melanoma cells.”

In results recently published in the US journal Cancer Research, Professor Zhang argues the protein drives melanoma proliferation independently of other cancer causing factors such as genetic mutations.

“This therapy could potentially result in better long-term outcomes for more people, which is urgently needed,’’ he said.

“Because it’s right at the top of many pathways and we have mapped the site responsible I believe we can design some highly targeted inhibitors for RIP1, to switch off its pro-survival mechanism but leave its pro-death function intact … this will limit the side-effects.”

The new discovery is likely to lead to future collaborations with the world’s top cancer researchers.

The news is particularly significant for the Hunter, which has above average rates of melanoma.

Cancer Institute NSW figures show the Hunter ranks fourth in a list of five red-zone regions behind northern NSW, the mid-north coast, the Central Coast and ahead of northern Sydney.

A list of 28 local government area red zones lists Port Stephens at number 12, Lake Macquarie at 16 and Newcastle at 26.

The institute estimates more than 4000 people in NSW will be diagnosed with life-threatening melanoma this year.