Researchers develop new class of cancer drug with potential to treat leukaemia
Scientists have hailed “a new era for cancer therapeutics” as they take a step towards developing a new drug for treating a rare blood disorder, myeloid leukaemia.
University of Cambridge researchers have reported a new approach to cancer treatment that targets enzymes which play a key role in translating DNA into proteins and could lead to a new class of cancer drugs.
Genetic code is written in DNA, but in order to generate proteins – molecules that are vital to the function of living organisms – DNA first needs to be converted into RNA.
The production of proteins is controlled by enzymes, which make chemical changes to RNA.
However, occasionally these enzymes become mis-regulated, being produced in over-abundance.
In a study published in 2017, a team led by Professor Tony Kouzarides, from the Milner Therapeutics Institute and the Gurdon Institute at the University of Cambridge, showed how one such enzyme, METTL3, plays a key role in the development and maintenance of acute myeloid leukaemia.
It is over-produced in certain cell types, leading to the disease.
Acute myeloid leukaemia (AML) is a cancer of the blood in which bone marrow produces abnormal white blood cells known as myeloid cells.
These normally protect the body against infection and against the spread of tissue damage.
AML grows rapidly and aggressively, usually requiring immediate treatment, and affects both children and adults.
In the UK around 3,100 people are diagnosed with the condition every year, the majority of whom are over the age of 65.
Now, Prof Kouzarides and colleagues at the University of Cambridge, Storm Therapeutics, a Cambridge spinout associated with his team, and the Wellcome Sanger Institute have identified a drug-like molecule, STM2457, which can inhibit the action of METTL3.
In tissue cultured from individuals with AML and in mouse models of the disease, they showed that the drug was able to block the cancerous effect caused by over-expression of the enzyme.
Prof Kouzarides said: “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.”
Researchers tested the drug on cell lines derived from patients with AML and found that it significantly reduced the growth and proliferation of these cells.
According to the study published in the journal Nature, it also induced apoptosis – cell death – killing off the cancerous cells.
The researchers transplanted cells from patients with AML into immunocompromised mice to model the disease.
When treated with STM2457, they found that it impaired the proliferation and expansion of the transplanted cells and significantly prolonged the lifespan of the mice.
It also reduced the number of leukaemic cells in the mouse bone marrow and spleen, while showing no toxic side-effects, including no effect on body weight, the study suggests.
Dr Konstantinos Tzelepis, from the Milner Therapeutics Institute at the University of Cambridge and the Wellcome Sanger Institute, said: “This is a brand-new field of research for cancer and the first drug-like molecule of its type to be developed.
“Its success at killing leukaemia cells and prolonging the lifespans of our mice is very promising and we hope to begin clinical trials to test successor molecules in patients as early as next year.
“We also believe that this approach – of targeting these enzymes – could be used to treat a wide range of cancers, potentially offering us a new weapon in our arsenal against these terrible diseases.”
The research was supported by Cancer Research UK, the European Research Council, Wellcome, the Kay Kendall Leukaemia Fund, and Leukaemia UK.