Susanna Greer: Next target – neuroblastoma
Susanna Greer, Chief Scientific Officer at The V Foundation for Cancer Research, shared on LinkedIn: .
“Pediatric cancers, including neuroblastoma, often occur because cells don’t develop correctly. Neuroblastoma is the most common solid tumor in children, forming in the nervous system. Despite aggressive treatments like surgery, radiation, and chemotherapy, the survival rate for high-risk neuroblastoma is only about 50%. This makes our finding better treatments for neuroblastoma a top priority.
This week’s Cool Cancer Find takes us to the Lab of Dr. Kimberly Steigmaier a the V Foundation at Dana-Farber Cancer Institute who studies the genes that drive neuroblastoma, and specifically a gene called MYCN, which can make neuroblastoma cancers grow more aggressively. Directly targeting MYCN is very difficult, so researchers like Dr. Steigmaier have been looking for other ways to disrupt its effects. One promising approach is to target groups of proteins called histone-modifying complexes. These complexes can change how DNA is packaged in cells, affecting which genes are turned on or off.
Histone-modifying complexes, like the SAGA complex, are essential because they help control gene activity. The SAGA complex includes proteins like KAT2A and KAT2B that add chemical groups to histones (the proteins around which DNA is wrapped), which can turn genes on or off. By targeting these proteins, researchers aim to disrupt the cancer’s growth.
Dr. Steigmaier and her team used advanced screening techniques, called CRISPR-Cas9 technology, to simultaneously study the roles of thousands of genes in neuroblastoma. They found that the SAGA complex is crucial for the growth of MYCN-amplified neuroblastoma. By inhibiting the activity of KAT2A and KAT2B using a special molecule known as a degrader, the researchers could slow down or stop the growth of neuroblastoma cells in lab models.
Why is this cool? Well, this treatment led to significant reductions in tumor growth, showing that the SAGA complex is a promising new target for therapy. Neuroblastoma is challenging to treat because it often returns even after aggressive treatment. This study is important because it identifies a new potential target for therapy in the SAGA complex. By better understanding how these complexes contribute to neuroblastoma, Dr. Steigmaier and her team hope to develop more effective and precise treatments for children with this cancer. This could improve survival rates and quality of life for young patients, offering new hope in the fight against this tough disease.
Read Dr. Steigmaier‘s paper here. Find out more about her lab.”
Source: Susanna Greer/LinkedIn