In the brains of babes
Dr. Jennifer Chan uses insights about normal brain development to understand pediatric brain cancers.
Story by Julie Sedivy/Illustration by Blair Kelly
Dr. Jennifer Chan has two children aged three and five years. Like many parents, she enjoys watching the rapid changes and new skills that come with her children's burgeoning brain development. But as a clinician and medical researcher who specializes in brain cancers, she also has a front-row seat to the darker side of children's blossoming brain power.
For a few children, the complicated biochemical timing sequences that are part of normal brain development go awry, leading to the growth of malignant brain tumours. Medulloblastoma is the most common of these malignant childhood tumours, and 40% of children with this type of tumour are diagnosed before the age of five. If they are not treated, medulloblastomas spread quickly throughout the brain and spinal cord. To Dr. Chan, understanding the complex chain of events in the normally developing brain is key to understanding how malignant tumours invade a child's nervous system.
Medulloblastoma crops up in the cerebellum, an area at the back of the brain just above the brainstem. It tends to occur at a very young age precisely because that's when cells in this part of the brain are proliferating quickly. The same conditions that allow brain cells to multiply can also lead to cancerous cells growing out of control. Normally, the brain has ways of putting the brakes on the growth of abnormal cells. But when something goes wrong with this system of regulation, malignant brain tumours can grow unchecked.
Dr. Chan is interested in how growth in the brain is controlled. One area of her investigations builds on Nobel-prize-winning work by scientists Andy Fire and Craig Mello on a class of regulatory genetic material known as small interfering RNAs and micro-RNAs. Although very small, these RNAs can control the translation of the genetic code of DNA into proteins and affect proteins involved in many different processes such as how cells carry oxygen, fight disease, or allow brain cells to communicate with each other. It's critical that the right amount of each kind of protein is produced—too much or too little can lead to cancers or other diseases. Dr. Chan has noted that, normally, very high levels of certain micro-RNAs can be found at critical points in brain development. This has led her to explore whether micro-RNAs play a role in preventing the growth of malignant tumours in the brain.
It seems that they do. In medulloblastomas, Dr. Chan has found much lower levels of these key micro-RNAs in comparison to healthy brains. What's more, once cells have become cancerous, re-introducing micro-RNAs into the cells actually slows down tumour cell growth. Dr. Chan likens the approach to re-activating a safety brake that has stopped working.
Although treating human brain tumours in this manner is still in the future, Dr. Chan believes it could be a promising brain cancer therapy. Currently, radiation therapy is the most effective way to treat pediatric tumours. But because the patients' brains are often still developing, radiation treatment can disrupt that development, leading to long-term neurological problems. Re-introducing micro-RNAs into cells could be a less toxic way to control tumour growth. And if micro-RNAs could slow the growth of a tumour or delay its recurrence after surgery, doctors could postpone radiation therapy until the child's brain has had more time to mature.
The convergence between basic research in brain development and the promise of possible cancer treatment is more than just coincidence for Dr. Chan. She sees her role as linking basic scientific research and clinical practice, and she chooses to place her energies where she thinks she is likely to make such connections. As for her particular interest in pediatric brain tumours, she acknowledges that having young children may have something to do with it—her current research allows her to indulge a mother's fascination with a child's rapidly developing brain.