Australian researchers at the Children's Cancer Institute have pinpointed a critical cellular protein, ALYREF, that drives the development of neuroblastoma—one of the most common and lethal cancers in young children.
Neuroblastoma, a cancer of the nervous system, is among the most frequent solid tumors in children. It exhibits wide clinical variability, from spontaneous regression without intervention to rapid, fatal progression.
About one-third of children with elevated MYCN levels—a transcription factor that boosts genes promoting neuroblastoma growth—face poor prognoses. Yet MYCN has long been an elusive drug target.
For years, experts have targeted MYCN-interacting molecules. In a landmark study published in Nature Communications, scientists from the Children's Cancer Institute in New South Wales, Australia, zeroed in on ALYREF.
Their findings reveal ALYREF binds directly to MYCN, activating USP3 to stabilize it and sustain the high MYCN levels essential for cancer progression.
MYCN's reliance on ALYREF for cancer cell proliferation makes it a prime inhibition target, potentially halting this vicious cycle. Co-author Dr. Glenn Marshall calls it a "worldwide discovery."
"We showed for the first time that ALYREF binds and controls MYCN in neuroblastoma cells," Dr. Marshall explains. "This gives us a new molecule to target—a fresh way to block MYCN and stop aggressive cancer growth."
The team now aims to develop drugs inhibiting ALYREF for clinical trials in children with high MYCN and ALYREF tumors.
Targeting ALYREF could also benefit other MYCN-driven cancers, including certain blood cancers, glioblastoma, retinoblastoma, and neuroendocrine prostate cancer.
