Preclinical cancer therapy leads to shrinking neuroblastoma
A cell protein known as MYCN (v-myc avian myelocytomatosis oncogene), one of a group of proteins that spur cellular proliferation, is known to be very resistant to even targeted drug treatments, but preclinical research is turning this protein on itself to fight off new neuroblastoma cancer growth, the Dana Farber Cancer Institute and Boston Children’s Hospital announced today.
Neuroblastoma is the most common cancer among infants and accounts for up to 7 percent of all cancers in kids and 15 percent of all deaths from pediatric cancer, according to Dana Farber stats.
Rani George, MD, and colleagues from the Cancer Center and Boston Children’s took animal models of neuroblastoma and an investigational compound called THZ1 that turns off the regulation of proliferation once it binds to a protein called CDK7. Not only that, but it is able to affect the regulation of growth in other proteins, as well. The results revealed smaller tumors and no serious collateral damage.
"Because normal cells don't acquire super-enhancers on these master regulators, the agent had a profound impact on neuroblastoma tissue but not on normal tissue," said George in the press release. "We've shown that it is possible to stifle MYCN itself as well as the effects of MYCN amplification."
MYCN and its group of transcription factors, including CDK7, connect to DNA and moderate the genetic information being accessed inside the cell. A drug that targets this mechanism could be a boon for the treatment of neuroblastoma.
"Recent studies have shown that when transcription factors like MYCN are mutated or overabundant, they can have a cancerous effect,” added Edmond Chipumuro, PhD, also from the Dana-Farber Cancer Institute. “They cause a global rise in gene expression, making genes throughout the cell more active. Because transcription factors have proven so difficult to block with targeted therapies, we wanted to see if an alternative approach that targets these defective transcriptional mechanisms would be effective."
A THZI drug is currently being developed for future clinical trials in humans.