Barts Cancer Institute teams awarded nearly £3m from Cancer Research UK to seek novel cancer therapy targets
Congratulations to Professor Michelle Lockley and Dr Oliver Pearce, who have both been awarded prestigious Programme Foundation Awards from Cancer Research UK, worth nearly £1.5 million each, to support the work of their research groups at Barts Cancer Institute, Queen Mary University of London.
In this funding round, only two Programme Foundation Awards were awarded across the UK — both to researchers at Barts Cancer Institute.
Professor Lockley’s programme will investigate how ovarian cancers develop resistance to treatment, while Dr Pearce’s team will study how changes to the cellular scaffolding surrounding tumours affect the immune system’s response to cancer. Over the course of these six-year programmes, both groups aim to identify new therapeutic targets that could be taken forward into future clinical studies.
We spoke to Professor Lockley and Dr Pearce about the challenges they are tackling and how the new funding will support their research.
Professor Michelle Lockley
Tell us about the challenges you are tackling.
Over time, almost all cancers evolve resistance to cancer drugs. In our lab, we want to understand how this resistance develops and how it is influenced by the drugs we give. If we can understand this process better, we may be able to slow the development of resistance and keep cancer under control for longer.
My research focuses on ovarian cancer. Unfortunately, around 80% of women with ovarian cancer see their cancer return after treatment because it has developed resistance.
How will you address these challenges with the new grant?
We’re currently running a clinical trial called ACTOv in lots of hospitals around the UK. ACTOv is studying an approach known as adaptive therapy in women with ovarian cancer. In this approach, doses of the chemotherapy drug carboplatin are adjusted according to how each patient’s cancer grows and shrinks over time. The aim is to keep the tumour at a manageable level for longer and prevent resistance from developing.
As part of the trial, we are collecting a series of blood samples and tumour biopsies from patients receiving different drug doses. In the biopsy samples, we will use a technique called spatial transcriptomics, which allows us to map how gene activity changes in different regions of a tumour and its surrounding environment during treatment. This work will enable us to understand how resistance evolves and is shaped by drug therapy, while the blood samples will allow us to measure this evolution over time.
In addition to these genetic changes, previous studies from my lab and others have shown that the extracellular matrix — a network of proteins that surrounds and supports cells — changes as cancer progresses. Certain changes appear to create an environment that helps protect cancer cells from the effects of chemotherapy. What I’m interested in is understanding how these changes arise, how they protect the cancer, and how we might disrupt this process to help treatments remain effective for longer.
How could this work benefit patients?
We hope to understand how different drug doses influence the development of resistance and identify ways to track resistance as it evolves, including by analysing blood samples.
This could help clinicians use existing therapies in a more tailored way, adjusting drug doses and treatment schedules to keep a person’s cancer under control for longer.
Our research may also reveal changes in the extracellular matrix that could be targeted with new therapies to address treatment resistance. This is an area where we plan to collaborate closely with Oliver and his team.
Our vision is to begin developing clinical trials alongside the research funded by this grant, so that we are ready to launch these new studies towards the end of the programme. These might include the next generation of adaptive therapy trials, new treatments targeting the extracellular matrix, or potentially combinations of both approaches.
Dr Oliver Pearce
Tell us about the challenges you are tackling.
The extracellular matrix — the network of proteins that surrounds cells — has a major influence on how tumours develop and how the immune system responds to them.
In some cancers, the matrix forms a dense barrier that makes it difficult for immune cells to enter the tumour and recognise cancer cells. This can limit the effectiveness of potentially valuable immunotherapies, which rely on supporting the immune system to identify and destroy cancer cells.
Our lab is particularly interested in pancreatic and breast cancers, where the matrix is often especially dense and difficult for immune cells to penetrate.
How will you address these challenges with the new grant?
The extracellular matrix is incredibly complex. This grant will help us untangle that complexity and understand how specific components of the matrix regulate interactions between tumours and the immune system.
We suspect that the location of different features within the matrix may be more important than how abundant they are overall. To explore this, we will use spatial analysis approaches that allow us to map changes within tumours while combining multiple types of data — including genes, proteins and chemical modifications to proteins.
We will test how these changes affect tumour and immune cell behaviour using tumour models that we grow in the lab. These models recreate key features of the tumour environment, including the extracellular matrix, immune cells and blood vessels.
How could this work benefit patients?
Ultimately, we hope to develop treatments that alter the tumour environment in ways that allow immune cells to enter the tumour more easily and recognise cancer cells. These approaches could be used alongside immunotherapies to improve how well they work.
By the end of the six-year programme, we hope to have several potential treatments that we are testing in preclinical studies. We have already identified a small number of promising candidates that we are actively investigating in the lab.
We are also collaborating with several biotechnology partners. For example, with Neobe Therapeutics we are exploring the use of microorganisms to deliver enzymes that modify the tumour extracellular matrix. In addition, with Anomer Bio, we are studying small molecules that alter chemical modifications on proteins within the extracellular matrix, which may have important effects on how the immune system responds to tumours.
Category: General News
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