Scientists developing new class of drug for leukaemia

In collaboration with the Press Association

Scientists are developing a new drug for treating acute myeloid leukaemia (AML), a type of blood cancer that affects around 3,100 people in the UK each year. 

The new approach, part-funded by Cancer Research UK and published in Nature, targets a key step in a cell’s ability to produce proteins and could lead to a new class of cancer drug. 

While still at an early stage, scientists are encouraged by the lab results so far and hope to begin clinical trials to test the drug in people with AML as early as next year.

"This work is yet another example of how our researchers strive to get new cancer treatments into the clinic and improve outcomes for cancer patients.” – Michelle Mitchell, chief executive of Cancer Research UK

Targeted treatment

The new approach stems from a 2017 study led by Professor Tony Kouzarides from The Milner Therapeutics Institute and the Gurdon Institute at the University of Cambridge, where researchers isolated a molecule that plays a key role in the development and progression of AML, called METTL3.

What does METTL3 do? METTL3 is an enzyme that plays a key role in regulating the production of proteins within the cell. A multi-step and tightly controlled process, protein production first involves reading a section of the cell's DNA and converting the code into an intermediary messenger, mRNA. It's at this step that METTL3 comes in, making changes to the mRNA. 

Taking this target forward, Kouzarides and colleagues at STORM Therapeutics have now identified a new drug, STM2457, that can stop the METTL3 enzyme from working properly.

“Until now, no one has targeted this essential process as a way of fighting cancer. This is the beginning of a new era for cancer therapeutics,” said Kouzarides.

Promising pre-clinical results

Initial research conducted on cells derived from patients with AML and grown in the lab found the drug significantly reduced cancer cell growth and killed AML cells. 

Studies involving mice with AML cells transplanted from patients provided further evidence of STM2457's potentialy benefits. The drug reduced the number of cancerous cells in the bone marrow and spleen, and significantly prolonged the lifespan of the mice. STM2457 was also found to produce no toxic side effects in the mice.

Based on these results, scientists hope to begin clinical trials to test the drug in patients as early as next year.

"We look forward to seeing the outcomes of the phase 1 trial and the benefits it may have for people with AML and their families in the future," said Mitchell.

References

Yankoka, E, et al. (2020) Small molecule inhibition of METTL3 as a therapeutic strategy for acute myeloid leukaemia. Naturehttps://doi.org/10.1038/s41586-021-03536-w