Dr Stefan Bjelosevic's research has shown that acute myeloid leukaemias with FLT3-ITD mutations rely on the amino acid serine to survive and grow.

Dr Bjelosevic's work was one of many Peter Mac research projects presented at Lorne Cancer Conference 2022 last week.

"Thirty per cent of all acute myeloid leukaemias (AMLs) have a FLT3 mutation of some kind," says Dr Bjelosevic. "And traditionally these leukaemias have been harder to treat, leading to worse outcomes for patients."

The specific mutation Dr Bjelosevic and his colleagues were looking at – FLT3-ITD – is the most common type of FLT3 mutation.

While much work has been done developing drugs that directly thwart FLT3 mutations, inevitably the cancer cells become resistant to these drugs, which is why Dr Bjelosevic and his co-authors were keen to find an alternative mechanism to target.

"We've known since the 1920s that metabolism in cancer cells is very different to metabolism in normal cells," says Dr Kristin Brown, a senior-co-author on the study.

"However, it's only in the last 10 to 15 years that we've realised that these changes in metabolism aren't simply a bystander of cancer development, but directly drive it."

This reprogrammed metabolism in cancer cells enables them to grow faster and live longer than normal cells.

Researchers are keen to discover how these differences in metabolism can be harnessed to develop new cancer therapies.

In this study, they found that FLT3-ITD-driven AMLs were highly dependent on the amino acid serine, which can be produced by each and every cell in the human body.

"Leukaemia cells produce more and more serine, because they're addicted to it," says Dr Brown.

"But if we can cut off their ability to produce serine, that not only renders them more sensitive to other drugs like standard of care chemotherapy agents, it also directly inhibits their growth and survival."

The next step is developing potent inhibitors of this serine metabolism pathway that could then be trialled in patients, and looking at how this pathway may be important for other mutations or cancer types.

"This is one of the first studies that's really looked more in depth at the metabolic changes that are happening to allow AML cells to grow faster," says Dr Bjelosevic.

Dr Brown agrees: "Cancer metabolism was ignored for a long time. The more fundamental research we can do in this area, the greater chance we have to find new drug targets, and new ways to treat cancer."

"Studies like this really prove that studying cancer metabolism isn't just something of interest in the lab, it can be truly impactful."