A complex biobank of living tumours is helping researchers understand more about childhood cancer and leading to faster and more effective treatments.
The biobank is being developed by the Hudson Monash Paediatric Precision Medicine Program, supported by the Children’s Cancer Foundation, which is providing more than $5 million over five years.
Dr Duncan Crombie is the Children’s Cancer Foundation Senior Organoid Specialist on the Program and together with the Children’s Cancer Foundation Senior Biobank Specialist, is in charge of establishing and maintaining the ground-breaking biobank at Hudson Institute of Medical Research.
Tissues and biopsies from children who have had cancer surgery are brought to the laboratory and that is where Duncan’s job begins.
“I harvest the cancerous cells from those tissues and I make three-dimensional and two-dimensional cell cultures from them,” he says.
“Organoids are three-dimensionally grown balls of cancer cells. By growing them in the three dimensions we are able to better reproduce how those cancers work in the body. They are better models of human disease.”
These living mini-tumours are then subjected to a complex and comprehensive, automated testing regime.
“We’re trying to work out for each patient what’s going to be potentially the best therapy,”
says Duncan, the programs Senior Organoid Specialist.
“We’re also trying to understand more about the biology of these cancers affecting the children.”
“At Hudson Institute we have a massive panel of about 2,200 different drugs that we can screen with these cells to work out which drugs are the cell-sensitive ones.
“And that gives us an idea about how to treat each patient and it also starts telling us what’s happening inside the cell that’s making it cancerous.”
The program at Hudson Institute is unique because as well as the complex drug screening regime, which is much bigger than most international studies, it also incorporates new genetic editing technology to screen the mini-tumour cells in the laboratory.
CRISPR technology (an acronym for “Clustered Regularly Interspaced Short Palindromic Repeats”) is a tool for editing genomes. It allows researchers to alter DNA sequences and change gene function.
“CRISPR allows scientists to very easily edit any part of the genome, any part of the DNA that provides instructions to the cells on how to work,” says Duncan.
“So this means that we can target any part of the genome and we can then identify which genes are essential for cancer growth. This is in addition to locating the disease-causing mutations in cancer cells through next-generation sequencing.”
“Everyone’s genetically different. This is why precision medicine is so important because it enables us to look at these differences in detail rather than providing a shotgun approach of one therapy for every child.
“The idea is that at the end of this process we can provide information that can be used by oncologists to inform their treatment decision.”
“The growing biobank of mini-tumours is a living resource that is a vital resource for researchers now and into the future. It’s a national and global effort,” says Duncan. “We’re really working with as many people as we can to find answers to effectively treat these tumours.”
“We receive patient tissues from Monash Children’s Hospital and the Royal Children’s Hospital in Melbourne, but we also culture cells from our collaborators in Australia and overseas.”
“Internationally we work with a large number of organisations, so we share a lot of data. That means we can access genetic information from thousands of patients from overseas.” “The number of therapeutically approved drugs is constantly growing. So we’ll be able to go back and screen cell lines that we’ve used in the past with these new drugs.”
“We can actually freeze the cells. Even years later we can bring them back out of the freezer and grow them again for further testing,” says Duncan.
Although the Program is still in its early stages, researchers hope they can establish a faster and more effective approach to treatment for childhood cancers.
“The significance behind precision medicine, is that we can very quickly on a patient-by-patient basis provide this really crucial information, which can inform clinicians as to patient specific treatment options.” says Duncan.
“Right now it’s a learning experience, but over the next several years, this program will hopefully lead to a better outcome for patients, reducing many of the long term side effects from standard treatment regimes.”
Photo Credit: Hudson Institute
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