Activating proteins may halt spread of lethal brain cancer

Scientists have found that activating a specific family of proteins can stop the spread of the most lethal and aggressive brain cancer.
Glioblastoma multiforme (GBM) is the most common brain tumour in adults. People with GBM often live fewer than 15 months following diagnosis because, despite surgery, radiation and chemotherapy, individual cancer cells escape and invade healthy surrounding tissue, making additional treatment attempts difficult.
"New therapies for GBM are desperately needed. We hope our latest finding will lead to a novel and effective treatment for this extremely aggressive cancer," said corresponding author Kathryn Eisenmann, assistant professor at the University of Toledo in the US.

The study expands upon an earlier discovery of a bioactive peptide called DAD and small molecules called intramimics, by Arthur Alberts, professor at Van Andel Research Institute in US.
Both DAD and intramimics activate a family of proteins called DIAPHs or mDIA, which are known to play vital roles in GBM spread.
Eisenmann's team, led by first author Jessica Arden, showed that locking DIAPH into an 'on' state using DAD, intramimic-01 and intramimic-02 stops GBM cells from invading normal brain tissue.

"Metastatic tumour cells are like any moving vehicle - all of the wheels need to be pointed in the right direction when power is applied," said Alberts, a senior author on the study.

"DIAPHs build the structures that hold and point all the wheels moving cells in the right direction," said Alberts.
"Dr Eisenmann's data suggests that DIAPH activation or 'agonism' locks all wheels into arbitrary directions, so no matter how hard you push the pedal down, the tumour cells won't move," he said.
Historically, therapies aimed at combating the spread of GBM focused on inhibiting mDIA, a member of the DIAPH family that is integrally involved in cell structure and tumour motility.
Earlier work in the Alberts Laboratory also showed that intramimics could impair tumour growth in colon cancer cells and that they could be a potential therapeutic option for other cancers as well.

Little work had been done on molecules that activate mDIA as an anti-GBM therapy, prompting the recent study comparing mDIA activation versus inhibition in GBM.
"GBM is lethal because it so effectively escapes and evades therapy," Eisenmann said.
"Our hope is this discovery will prove to be an anti-tumour strategy and one that will be safe and effective for patients," Eisenmann said.
The study was published in the journal Molecular Biology of the Cell.