黑料吃瓜资源

The brain cancer, glioblastoma, is a fierce and formidable opponent. Its millions of victims include Senator John McCain, President Biden鈥檚 son, Beau, and famed film critic Gene Siskel, to name just a few. Most patients succumb within two years and few make it past five, a statistic that hasn鈥檛 improved in decades due to lack of effective treatment options.

鈥淭he aggressiveness of glioblastoma is notorious,鈥� says 黑料吃瓜资源 (CSHL) Professor Alea Mills. 鈥淭he norm is to do surgery, treat with harsh drugs, and just hope for the best.鈥� But now, Mills and her colleagues have discovered in this deadly cancer a vulnerability, known as BRD8, that may finally lead to new treatment options and better patient outcomes.

The CSHL team recently solved a decades-old mystery surrounding glioblastoma鈥檚 aggressiveness by linking the BRD8 protein to another protein, named P53. A staple in the body鈥檚 natural cancer defenses, P53 prevents cells from overgrowing and turning into tumors. Almost all cancers depend on P53 becoming mutated and thus disabled. But weirdly, in the majority of glioblastoma cases, P53 is unscathed. 鈥淪o why does this cancer act like P53 is broken?鈥� asked CSHL postdoctoral fellow Xueqin Sun. This critical question led Mills鈥� team to discover that BRD8 had gone rogue in glioblastoma, crippling P53 in a completely new way.

BRD8 shuts down access to genes in chromosomes. If a gene is wound up tightly, it cannot be used鈥攊t鈥檚 as if it were 鈥渁sleep.鈥� Mills and her team revealed that BRD8 was inappropriately active in glioblastoma, keeping many of P53鈥檚 critical anticancer defenses at rest. When the researchers inactivated BRD8 via genome editing, P53鈥檚 鈥渁rsenal鈥� suddenly woke up and began blocking tumor growth.

鈥淚t鈥檚 like BRD8 is saying 鈥楴O ENTRY鈥� to P53鈥檚 tumor-preventing power, but when we hit BRD8 in the right way鈥攇o in there almost like a scalpel, but molecularly鈥攖he tumor is annihilated,鈥� Mills explains. She and her team implanted tumor cells from glioblastoma patients into mice and watched the tumors grow in the brain. When BRD8 was inactivated, P53 was unlocked鈥攖he tumors stopped growing and the mice lived longer.

The finding suggests that drugs targeting the heart of BRD8 could work against glioblastoma. Mills hopes her team鈥檚 discovery will help turn this deadly brain cancer into a treatable disease and for the first time in a generation, extend the life expectancy of patients who are diagnosed with it.

Written by: Luis Sandoval, Communications Specialist | [email protected] | 516-367-6826

Funding

Cancer Center Support Grant, 黑料吃瓜资源 and Northwell Health Affiliation, National Institutes of Health, the Darlene Carbone Brain Tumor Foundation, the Bradley Zankel Foundation, the Edward Davis Foundation

Citation

Sun, X., et al., 鈥淏RD8 maintains glioblastoma by epigenetic reprogramming of the P53 network鈥�, Nature, December 21, 2022. DOI: