Research projects

Reversing resistance to immune checkpoint inhibitors

Researcher
Dr Adam Hurlstone
Project period
Feb 2022 - Feb 2025
Country
Research Institute
The University of Manchester
Cancer types
Melanoma
Award amount
£204,192

Project aim

Dr Adam Hurlstone and his team are trying to understand how melanoma becomes resistant to treatments that help the immune system work against cancer, in order to make these drugs more effective for more patients.

Hope for the future

Treatments that help the immune system destroy cancer (immunotherapies) have proven an effective way to treat melanoma, especially in cases where the cancer has spread and few other options remain. However, many patients do not respond to immunotherapy, and the treatment can stop working in others over time.

Dr Hurlstone and his team are now trying to understand why some patients stop responding to immunotherapies. They hope that studying this process in more detail will help them find new drug targets that could make immunotherapies more effective, making them a better option for more people with advanced melanoma and for a longer period of time.

 

Meet the scientist

Dr Adam Hurlstone has enjoyed science and medicine for as long as he can remember – his favourite toys and books as a child were all themed around science! He is motivated to do research every day by the chance to discover new phenomena, imagining how that discovery could help people, and seeing the joy of discovery in his staff and students.

The science

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that work by alerting the immune system to cancer cells so that they can be destroyed. They are an effective treatment option for many cancers, including metastatic melanoma, however over time melanoma cells seem to be able to adapt to this treatment and they stop working. It is not yet very well understood why this happens.

Dr Adam Hurlstone and his team recently discovered that an enzyme called PARP14 seems to play a key role – the genes that code for PARP14 can even be used to tell how well melanoma cells would respond to ICIs. They are now using this knowledge to better understand how resistance to ICIs develops, and will investigate whether drugs that target the action of PARP14 could be used to make ICIs effective again. The team hopes that these insights will help improve how effective immunotherapies are, especially for patients with melanoma that has spread, but this knowledge could go on to benefit patients with other cancers.

Dr Adam Hurlstone wearing red shirt and looking at camera Dr Adam Hurlstone
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