Those who suffer the most common childhood cancer, acute lymphoblastic leukaemia (ALL), generally face good treatment results. Most, but not all, will experience positive outcomes.
But ‘most’ is not good enough, says Professor Richard Lock, Head of the Leukaemia Biology Program at the Children’s Cancer Institute and Deputy Director of the UNSW Centre for Childhood Cancer Research.
“There are some children who are in high risk categories or who simply don’t respond well to their initial treatment for one reason or another,” Lock explains. “We are trying to understand why these leukaemias are resistant, or become resistant, to conventional treatment.”
“In developing this knowledge, we can help devise new treatments that can overcome that drug resistance and that can lead to improvements in outcomes for those children in the high risk category.”
Lock’s research program, funded by The Kids’ Cancer Project since 2017, is focusing on sub-types of paediatric ALL in which children respond poorly to treatment.
Read more: Reversing glucocorticoid resistance in paediatric acute lymphoblastic leukaemia
He and his colleagues are trying to understand molecular mechanisms. They’re drilling down at a single cell level to find out what is going on within the nucleus of the cell.
“We’ve carried out a detailed molecular analysis of the organisation of the DNA within drug resistant cells,” he says. “We have looked at how that might be altered in those drug resistant cells using contemporary molecular biology techniques. Essentially, we are comparing the DNA in the drug resistant cells to that in cells that are drug sensitive.”
“We have looked across the whole genome in a very detailed sense to identify new mechanisms by which these leukaemia cells might become resistant. There are multiple mechanisms by which a leukaemia cell might develop drug resistance, and by using this analysis in this project we have identified another novel mechanism of resistance.”
A paper outlining the outcomes of Lock’s research has been published in the esteemed American medical journal Cancer Cell. This publication, Lock says, is recognition of the quality of the work that was funded by The Kids’ Cancer Project and Cancer Australia’s Priority-driven Collaborative Cancer Research Scheme.
What comes next?
The joy and curse of brilliant research is that in introducing valuable new knowledge to the scientific and medical communities, scientists also then realise how much more there is to know.
For example, one part of Professor Lock’s research has involved the carrying out of drug screens to identify new molecules that could reverse drug resistance. He and his team have identified established drugs that could be used in combination, in an attempt to overcome drug resistance. That is one aspect of the project that must now be further pursued in order to produce potentially powerful results.
Also, Lock says, there is exciting opportunity in the fact that he has been doing detailed molecular analysis at the single-cell level.
“We can actually look at heterogeneity within leukaemia cell populations,” he says. “Rather than just looking at the average of thousands of cells, we can drill down and look at individual cells by single cell sequencing and single cell molecular analysis, etc. That is one of the two central areas of our future research.”
Of course, all of this relies heavily on funding. Lock has seen many promising and potentially powerful research projects fall over because the researchers were unable to win grants.
“Everybody in the lab is in a grant-funded position,” he says. “A lot of people don’t seem to understand how competitive it is to get research funding. They think a scientist writes the grant and submits it and then they automatically get the money. They don’t realise there’s perhaps a one in 10 chance of the grant application being funded.”
“There’s a lot of great research in Australia that doesn’t get funded because it is so competitive. That’s your life as a scientist, and unfortunately I see a lot of promising younger researchers who just say they can’t do this, and they go off and do something else. That’s a huge loss for everybody.”
A passion for kids’ cancer research
Now a respected leader in kids’ cancer research, Lock says there was not a single moment that drew him into the field. He had simply always been involved in childhood cancer research and he still feels it is where he belongs.
“When you have children of your own and then you have grandchildren, as I do, you really treasure the value of this sort of work,” he says. “And I think to be involved in childhood cancer research is as rewarding, and probably more rewarding, than any other field of cancer research.”
“I couldn’t say that I’ve ever been directly affected by childhood cancer, but I have always had a passion for this work. I think I am in exactly the right field, and I have been for the past 22 years.”