A new targeted treatment for anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) is a cancer that normally affects children and young adults. Most of these patients can be treated with a combination of chemotherapy drugs. Unfortunately, around 15% of patients cannot be treated successfully and die within five years. Three in ten patients also need to have several cycles of additional treatment that has difficult side-effects. We need less toxic treatments so that patients’ chance of survival, and quality of life, are improved. 

Scientists have created ‘targeted’ drugs, called ALK inhibitors, that stop cells from making the ALK protein, which can be needed for the growth of ALCL. These have fewer side effects, but sometimes don’t work because the ALCL cells don’t need the ALK protein, or the cells develop resistance. This means that we still need more treatment options. 

The research team at the University of Cambridge, led by Dr Isaia Barbieri, have studied how changes in the genetic code play a role in cancer. They found another type of protein that leukaemia cells need to grow. These proteins are responsible for a specific change to the genetic code, called METTL3. After discovering this protein could stop leukaemia cells from growing, they have found early data showing that stopping METTL3 activity could also stop other cancers like ALCL from growing. 

In this project, the researchers will investigate how stopping METTL3 activity affects ALCL, and test new drugs designed to stop activity, called METTL3 inhibitors. They will investigate the how well METTL3 inhibitors work when used on their own or in combination with another targeted drug called an ALK inhibitor. These are used to treat patients when their cancer needs the ALK protein to grow. However, sometimes patients treated with only ALK inhibitors become resistant to them. Dr Isaia Barbieri hopes that using METTL3 inhibitors alongside the ALK inhibitors could prevent patients from becoming resistant to the ALK inhibitors. In addition, the researchers will assess whether METTL3 inhibitors can overcome resistance to ALK inhibitors. This would enable more children and young adults to receive successful treatment with fewer side effects.