Scientists from Washington University School of Medicine in St. Louis have suggested a new approach to kill paediatric brain tumours.
During the study, the research team robotically “fired” 2,000 compounds into culture plates containing tumour cells to see if the compounds had any effect.
When the robotic screener found one substance had scored a hit by inhibiting growth of the tumour cells in its plate, researchers analysed what that compound acted against. Follow-up studies showed that the drug slowed tumour growth in mice by inhibiting the function of a protein called STAT3.
The findings would help in developing new drugs for the treatment of cancer in neurofibromatosis-1 (NF1), a genetic condition that causes increased risk of benign and malignant brain tumours.
“We were excited to find that the slowed tumour growth we observed following treatment resulted from increased tumour cell death – an effect we hadn’t seen before when we blocked other NF1 growth control molecules,” said senior author Dr David H. Gutmann, the Donald O. Schnuck Family Professor of Neurology.
“Now we can identify the genes that STAT3 influences to fine-tune our treatments and ensure that we kill cancer cells with minimal harm to normal cells,” Gutmann added.
Cucurbitacin-I, the compound that led scientists to STAT3, is a plant steroid. It belongs to a family of bitter-tasting compounds previously identified as inhibitors of STAT3.
After the successful robotic test of cucurbitacin-I, researchers showed that STAT3, which turns on and off the activity of a number of genes, is unusually active in NF1 tumor cells.
Further investigation revealed that STAT3 activity is regulated by another gene very familiar to Gutmann: the mammalian target of rapamycin (mTOR).
The results appear in the journal Cancer Research. (ANI)
