Experimental enzyme inhibitor could herald new class of cancer drug

Experimental enzyme inhibitor ...
A microscope image of human cells with acute myeloid leukemia (AML)
A microscope image of human cells with acute myeloid leukemia (AML)
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A microscope image of human cells with acute myeloid leukemia (AML)
A microscope image of human cells with acute myeloid leukemia (AML)

Scientists at Cambridge have demonstrated a new method for potentially fighting a form of leukemia, by targeting overactive enzymes that can lead to the disease. If the results of mice tests carry across to humans, it could be the first of a new class of cancer drugs.

Acute myeloid leukemia (AML) is an aggressive blood cancer with generally bleak outlooks. It affects a type of stem cell called a myeloblast, which is supposed to differentiate into white blood cells called myeloids. But in patients with AML, the myeloblasts freeze in their immature state, and begin to build up in the bone marrow.

In recent studies, researchers uncovered one of the pathways that leads to the disease. The production of proteins is encoded in the DNA of cells, and enzymes transcribe it into RNA and use that to make proteins as needed. A particular enzyme, known as METTL3, was found to be overexpressed in patients with AML, leading to the development and progression of the disease.

In the new study, the Cambridge team identified a molecule called STM2457, which can inhibit METTL3. This could open up a brand new way to treat not just AML, but other cancers that get their start from misregulated enzymes.

“Proteins are essential for our bodies to function and are produced by a process that involves translating our DNA into RNA using enzymes,” says Professor Tony Kouzarides, lead author of the study. “Sometimes, this process can go awry with potentially devastating consequences for human health. 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.”

To test it out, the team grew cancer cells in the lab, taken from AML patients, and treated them with STM2457. Sure enough, the drug significantly stopped the spread and growth of the cancer, and killed them off.

Next, the researchers transplanted these AML-patient cells into mice. Similar benefits were seen – the spread and growth of cancer cells was slowed, and the mice lived longer than controls. Counts of cancerous cells in the bone marrow and spleen of the animals were also lower. Importantly, no toxic side effects were noted.

The team says that the next steps are to develop more advanced versions of the molecules, and test them in humans. Phase 1 clinical trials could begin as early as next year.

The research was published in the journal Nature.

Source: Cambridge University

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