Combination of drugs may help cure brain cancer

A combination of drugs may act as a "double-whammy" to brain cancer tumours, according to a new study that may lead to novel therapies to treat the disease.

Researchers at the Children's Hospital of Eastern Ontario (CHEO) in Canada found that a combination of drugs known as SMAC Mimetics and immune checkpoint inhibitors (ICIs) amplifies kill rates of cancer tumour cells in laboratory testing.

They also discovered a new mechanism by which the combination promotes long-term immunity against glioblastoma tumours. The combination therapy also proved to be highly effective against breast cancer and multiple myeloma."These findings represent a significant evolution in our research and the field of immunotherapy," said Robert Korneluk, professor at the University of Ottawa in Canada.

"We are the first in the world to show the synergistic tumour-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma," said Korneluk.

"You could say it takes two to tango. We believe that it takes a combination strategy to impact cancer cure rates," he said.In 2014, researchers discovered that combining SMAC Mimetics with immune stimulators or



live virus therapies had a synergistic or amplified tumour-killing effect that was greater than either agent on its own.

The new study shows that SMAC Mimetics also have a powerful synergistic effect with ICIs, relatively new drugs that are showing great promise in the clinic.SMAC Mimetics known as LCL161 and Birinapant were combined with ICI antibodies targeting PD-1 and CTLA-4 immune checkpoints.

"Two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and ICIs on patients with a variety of cancers," said Eric Lacasse, a scientist at the CHEO Research Institute.

"Although it could be years before any clinical trials begin for adults or children with the deadly brain cancer, glioblastoma, we're looking forward to seeing how scientific evidence from these experimental treatments adds to our knowledge," Lacasse said.

"This research heightens our understanding of the mechanics behind this double-whammy effect, which both enhances the immune response and weakens tumour cells to immune attack," said Shawn Beug from CHEO. The study was published in the journal Nature Communications.