Nature solves decades of puzzle: the original p53 was destroyed in a completely new way

Brain cancer, glioblastoma, is a fierce and formidable opponent
.
Among the millions of victims are Sen.
John McCain, President Biden's son and famed film critic Gene Siskell, most patients die within two years, and few survive beyond five years, a statistic that hasn't improved
for decades due to a lack of effective treatment options.

"Malignant gliomas are notorious for their aggressiveness," said
Professor Alea Mills of the Cold Spring Harbor Laboratory (CSHL).
"The conventional thing is to have surgery, treat it with strong drugs, and hope for the best
.
" But now, Mills and her colleagues have identified a vulnerability in this deadly cancer known as BRD8, which could eventually lead to new treatment options and better patient outcomes
.

The CSHL team recently solved the mystery that has surrounded the aggressiveness of glioblastoma for decades by linking the BRD8 protein to another protein called P53
.
P53 is a major component of the body's natural cancer defense system, which prevents cells from overgrowing and turning into tumors
.
Almost all cancers rely on mutation and failure
of P53.
But strangely, in most cases of glioblastoma, P53 emerges unscathed
.
"So why does this cancer behave like P53 is destroyed?" This critical question led Mills' team to discover that BRD8 was out of control in glioblastoma, destroying P53
in an entirely new way.

BRD8 shuts down access
to genes in chromosomes.
If a gene is tightly wound, it cannot be used – as if it were "asleep"
.
The team found that BRD8 is abnormally active in glioblastoma, keeping many of P53's key anti-cancer defenses quiescent
.
When the researchers inactivated BRD8 through genome editing, P53's "arsenal" suddenly woke up and began to stop tumor growth
.

"It's like BRD8 saying 'NO ENTRY' to P53's tumor-preventing capabilities, but when we attack BRD8 in the right way — almost like a scalpel into there, but molecularly — the tumor is wiped out
.
" She and her team implanted tumor cells from glioblastoma patients into mice and watched the tumors grow
in the brains.
When BRD8 was inactivated, P53 was unlocked — tumors stopped growing and mice lived longer
.

This finding suggests that drugs that target the BRD8 heart may be effective for
glioblastoma.
Mills hopes her team's findings will help turn this deadly brain cancer into a treatable disease and extend the life
expectancy of patients diagnosed with the disease for the first time in a generation.