Scientific advancements have seen an increase in survival rates for the most common form of childhood cancer but, for some kids, conventional treatment is proving unsuccessful.
Dr Diane Hanna, paediatric oncologist at Melbourne’s Royal Children’s Hospital and researcher at the Walter and Eliza Hall Institute of Medical Research, is committed to developing a novel approach to treatment that is tailored precisely to this group of children.
“We know that there's only so much chemotherapy that we can give to a child,” said Dr Hanna.
“It's about identifying those patients that are refractory, or resistant, very early in their disease trajectory, and then using novel compounds, either as a bridge to transplant, or a bridge to other kinds of definitive therapy.”
Acute lymphoblastic leukaemia (ALL) is the most common form of childhood cancer. Dr Hanna’s research focuses on particular sub-types of the disease that are resistant to chemotherapy. These subtypes are driven by proteins in the cells known as kinases.
“The kinase in the leukaemia cell is like the gas pedal that drives the leukaemia’s growth,” Dr Hanna explained.
“There are some ALL subtypes that are higher risk based on the biology of the disease and patients in this high-risk bracket generally don’t respond to conventional treatment.”
Dr Hanna is narrowing in on ALL subtypes called Philadelphia chromosome-positive and Philadelphia-like ALL, which are high-risk kinase-activated subtypes.
“They are amenable to targeted therapy with kinase inhibitors, which bind to proteins and tell the cell to die, in theory,” she said.
“My project is about using novel molecules called BH-3 mimetics. There are different kinds that target different pro-survival proteins within the cell. Essentially, they tell the cell to die downstream of the kinase, either in combination with a kinase inhibitor or in combination with each other.”
A different perspective
Dr Hanna grew up in a family of engineers, but always knew she wanted to study medicine. One of her first rotations as a resident was in paediatric oncology and she formed a special connection with both the science and the children.
“We're in a very exciting time where the expectation is a cure for childhood leukaemia,” said Dr Hanna.
“We're in the molecular era where we can target tumours really well and use varying molecules in combination with chemotherapy to improve outcomes.”
Dr Hanna said her clinical work makes her time in the lab more meaningful.
“It gives me a different perspective as well. I have a lot of questions from the clinic that I want to answer.”
“In my role as a researcher, I can take them straight into the lab and then back to the clinic. There’s such a valuable interplay between the two roles. I also get to see the resilience of these kids in a clinical setting,” she said.
Preparing for trial
Dr Hanna’s study is currently at preclinical trial stage. She is transplanting human leukaemia into laboratory models to expand the leukaemia.
“I then put cells in a petri dish and apply various drug treatments to see how the cells die,” she explained.
Dr Hanna said her study is looking very promising and she is currently focusing on drug combinations to minimise side effects.
“I’ve set up toxicity assays in the laboratory to ensure that the combination of molecules is tolerable without significant side effects and I've been able to determine the maximum tolerated dose,” she said.
Dr Hanna said funding from The Kids’ Cancer Project has come at a “critical time.”
“This is the year where I'm able to tie up all the loose ends and move forward with answering some critical questions that will be helpful in developing early phase trials in the clinic,” she said.
Over the next six months, Dr Hanna plans to complete her lab research so that she can develop protocols for early phase clinical trials.
“These early phase trials will be with small numbers to demonstrate safety in a highly refractory subgroup of patients where other treatment modalities have failed,” she said.
“We expect BH-3 mimetics to be a really useful tool for getting these children into remission as a bridge to transplant, and that’s why we need to start exploring these kinds of novel approaches to treatment.”
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