Rogue protein that powers the deadliest brain cancers identified by scientists

More than 1,000 patients across the UK and Switzerland have been recruited for the trial (Alamy/PA) ((Alamy/PA))

A rogue protein that powers the deadliest brain cancers has been identified by scientists in a breakthrough that opens the door to its destruction.

Improved therapies are urgently needed for glioblastomas, an aggressive type of brain tumor that is often incurable.

Lead author Professor Alea Mills, from Cold Spring Harbor Laboratory in New York, said: ‘The aggressiveness of glioblastoma is notorious.

“The norm is to do surgery, treat with harsh drugs and hope for the best.”

But now the US team has found its “Achilles heel”: a molecule that helps diseased cells spread.

Known as BRD8, this discovery could finally lead to better treatment options and better patient outcomes.

Around 2,500 cases are diagnosed in the UK each year. Only seven percent of patients survive.

Millions of victims around the world have included Senator John McCain, President Biden’s son Beau, actors Robert Forster and Tim Conway, and famed film critic Gene Siskel.

Most succumb within two years and few survive beyond five, a statistic that hasn’t improved in decades.

Professor Mills and his colleagues hope the grim numbers are about to change after finally solving why glioblastomas are so aggressive.

They found that BRD8 paralyzes another protein called P53 – a building block of the body’s natural defenses against cancer.

It becomes overactive – crushing out the beneficial chemical that prevents cells from dividing and turning into tumors.

In experiments, researchers knocked out BRD8 using a pioneering gene-editing technique – waking up the “arsenal” of P53. The tumors were stopped in their tracks.

It raises hopes of curing glioblastomas by “editing” DNA in the brain with a drug – without any tissue having to be removed.

Almost all cancers depend on the mutation of P53 and therefore its deactivation. Curiously, in glioblastomas, it is unscathed.

Co-author Dr Xueqin Sun said, “So why is this cancer acting like P53 is broken? “. The study showed that BRD8 works in a unique way.

It closes access to genes in chromosomes, pieces of DNA inside cells. If a gene is tightly coiled, it cannot be used – it is as if it is “asleep”.

The researchers revealed that BRD8 was inappropriately active in glioblastoma – keeping P53 quiescent.

Professor Mills explained: “It’s as if BRD8 is saying ‘no access’ to the tumor preventing power of P53.

“But when we hit BRD8 the right way – go almost like a scalpel, but molecularly – the tumor is wiped out.”

The researchers implanted tumor cells from glioblastoma patients into mice and observed them in the brain.

When BRD8 was knocked out, P53 was unlocked – tumors stopped growing and rodents lived longer.

The findings in Nature suggest that drugs targeting the heart of BRD8 could work against glioblastoma.

Professor Mills hopes this will help turn deadly brain cancer into a treatable disease, dramatically extending patients’ lifespans.

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