(L) Mr Dani Tutuka, (Centre) Prof Jonathan Cebon, (R) Dr Andreas Behren

An unwanted side-effect of a standard treatment for advanced melanoma could be overcome by a new generation of anti-cancer compounds, scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) have found.

About half of all advanced melanomas have a mutation in a gene called BRAF which drives the proliferation of the cancer. It is standard for people with BRAF-driven melanoma to be treated with targeted compounds called BRAF inhibitors.

Although these BRAF inhibitors work in most people with BRAF-mutated melanoma and block signals leading to cancer cell proliferation, paradoxically, they can also inadvertently trigger the same signaling pathway in non-melanoma cells thereby promoting the development or growth of other secondary cancers, including colorectal cancers. To prevent this from happening patients are treated with a second compound that stops this cell signaling pathway from being unintentionally activated. However, this may not be enough to always prevent the emergence of secondary cancers or their precursors.

Dr Andreas Behren, who led the ONJCRI research team, said that although extremely rare, it couldn’t be predicted which melanoma patients might develop other cancers as a result of their treatment. “A new generation of BRAF-inhibiting compounds termed ‘paradox breakers’ has therefore been developed in the hope of avoiding these unwanted side effects,” he said.

Dr Behren, Prof Jonathan Cebon, Mr Dani Tutuka and others from the ONJCRI examined whether these new-generation BRAF inhibitors could be successfully used to treat melanoma patients without unintentionally accelerating the growth of other cancers, including colorectal cancers.

Their research is published in the current issue of the journal Molecular Cancer.

Dr Behren said the ‘paradox breaking’ compounds were tested on BRAF melanoma cells for their potential to inhibit their growth and, after being seen to successfully target these cells, were then tested for their growth-promoting effects on various colorectal cancer cells in comparison to the classical drugs.

“We found that these new-generation paradox-breaking BRAF inhibitors did not promote or accelerate the growth in the colorectal cancer cells and may therefore, pending the results from ongoing clinical trials, be a safer alternative to be used alone or in combination in melanoma patients,” Dr Behren said.

The research was supported by the Melanoma Research Alliance, the National Health and Medical Research Council of Australia, Cancer Council Victoria and the Victorian State Government Operational Infrastructure Scheme.