Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive paediatric brain tumour.
The tumour is always fatal and primarily strikes children under 10 years old.
Every year, about 300 children under the age of 10 years old in the U.S. develop a tumour referred to as diffuse intrinsic pontine glioma (DIPG).
"This tumour kills every single kid who gets DIPG within one year. No one survives," said the study's first author, Andrea Piunti, a postdoctoral fellow in Shilatifard's lab in biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.
The study is published in Nature Medicine.
"To the best of our knowledge, this is the most effective molecule so far in treating this tumour," said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Paediatrics and the chair of biochemistry and molecular genetics at Feinberg. "Every other therapy that has been tried so far has failed."
Radiation therapy only prolongs patients' survival by a few months, he noted.
Shilatifard's lab previously identified the pathway via which this mutation causes cancer in studies with fruit flies, which was published in Science a few years ago.
He and colleagues believed the pathway would be a good target to thwart the tumour and pushed forward with their molecular studies.
Shilatifard and Piunti collaborated with C. David James, Dr. Rintaro Hashizume, Dr. Craig Horbinski, Dr. Rishi Lulla and Dr. Amanda Saratsis at Northwestern Medicine.
Lulla, a paediatric neuro-oncologist, and Saratis, a paediatric neurosurgeon, respectively, are also at the Ann & Robert H. Lurie Children's Hospital of Chicago.
The scientists also are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
In a study with Hashizume's group, they demonstrated mice in the experiment, which had the drug delivered through their abdomen, had an increased survival of 20 days, which is a long time in the life of a mouse, Piunti said.
Now the team at Northwestern Medicine and Lurie Children's is working on delivering the drug to the brain stem to see if the effect will be more potent and effective.
To test the molecule, scientists took tumour cell lines from a paediatric patient that was untreated and injected those cells into the brain stem of a mouse.
The human tumour engrafted in the brain of the mouse.
The mouse was then treated with the molecule while scientists monitored the tumour.
The molecule stopped the growth of the tumour cells and forced them to turn into other types of cells, known as differentiation, thereby halting its growth.
This molecule detaches proteins, known as bromodomain proteins, from their binding to a mutant protein, the histone H3K27M, which is present in more than 80 percent of these tumours.
While the molecule itself is not yet available commercially, another similar class of molecules, BET inhibitors, is being tested in clinical trials for paediatric leukaemia and other types of tumours.
These could be used in a clinical trial for the paediatric tumour, Piunti said.
Source: Northwestern University
(27 Apr 2017)