Dr Simon Mitchell, a Leukaemia UK John Goldman Fellow, is using computer simulations to reveal new ways to treat diffuse large B-cell lymphoma. His work could lead to therapies that are personalised for individual patients, improving their chances of survival.

The challenge

Diffuse large B-cell lymphoma (DLBCL) is one of the most common blood cancers, and is caused by a wide variety of different mutations. Every person’s DLBCL is different, but despite this diversity, for over a decade people have tended to receive the same first-line treatments. Many will respond well to these treatments, but a significant proportion of patients still have very poor chances of survival.

We need new approaches to selecting treatments, to make sure each person gets the right drug for them, giving them the best chances of survival.

The science behind the research

Dr Simon Mitchell uses computer simulations to recreate diseases and perform virtual experiments on them. In previous work, he showed that computer simulations of B-cells – the healthy counterparts of DLBCL cells – accurately predicted how real B-cells respond to drugs in the lab.

In this John Goldman Fellowship project, he will do the same for DLBCL cells: simulating the mutations seen in actual DLBCL patients to create a diverse range of ‘virtual patients’. Simon will treat every drug target in every virtual patient, to predict the best drug for each one.

Simon will then cluster the virtual patients into groups that respond well to the same treatment. Then he will identify ‘biomarkers’ – a property of cancer cells that can be measured – to help decide for real patients which drug targets are the best for their disease.

What difference will this research make?

Simon’s work is an entirely different approach to selecting the right drugs for each person with DLBCL. By creating computer simulations of the disease, Simon aims to find promising new treatments that will target the ‘Achilles heel’ of each patient’s disease.

This work also lays the foundations for using virtual patients to help make treatment decisions in real time. Simon’s vision is that, when someone is diagnosed with lymphoma, a simulation is created of that patient, which is used to quickly perform virtual drug trials to find the best treatment option for them.

If this can be achieved, it will mean people with DLBCL receive targeted, personalised therapies that give them the best chance of survival, with fewer side-effects.