Developing bowel cancer immunotherapies that target DNA repair
Dr Antonio Porro aims to better explain the genetic changes underlying a condition called Lynch syndrome, which makes patients more likely to develop bowel cancer. They hope to find tools that can take advantage of this to improve immunotherapy treatment for cancer.
Hope for the future
Inherited conditions that increase a person’s risk of developing cancer account for around 10% of all cases of cancer. These cases are caused by changes, or mutations, to a person’s genes that make it more likely that a tumour will develop. Better understanding of the genes involved in these inherited conditions can lead to new ways to prevent, diagnose, or treat cancer.
Lynch syndrome is the most common cause of hereditary bowel cancer, and people with Lynch syndrome are more likely to get bowel cancer as well as certain other cancers including stomach cancer and liver cancer. Immunotherapy can sometimes treat bowel cancers caused by Lynch syndrome, but it does not work on everyone, and cancers can sometimes become resistant to this treatment.
Dr Antonio Porro wants to discover more about the genes involved in Lynch syndrome to identify ways to help immunotherapy work better. Moreover, he aims to go further and develop tools to use cancer immunotherapy in different types of tumours.
Meet the scientist
When the first near complete human genome was sequenced in the early 2000s, Dr Porro was immediately fascinated. This incredible discovery would go on to make whole new areas of research possible, and it was a huge driving force for Dr Porro as he went on to study genome instability and tumour progression.
Dr Porro is originally from Puglia in the south of Italy, and outside of the lab he continues his experiments with Italian cooking, as well as spending time with his children and planning their next big adventure.
Lynch syndrome is caused by mutations, including a specific mutation to a gene called MLH1. This gene normally helps fix mistakes made when DNA is copied. Interestingly, we experience damage to DNA thousands of times a day, but this damage is usually repaired without issue.
In the case of Lynch syndrome, mutations in the MLH1 gene mean that this repair process does not work, and DNA can become more and more damaged. This damage makes it more likely that cancer will develop and that treatments will be unable to cure the cancer.
The protein made by MLH1 has been shown to influence cancer development through its control of two enzymes, called EXO1 and FAN1. When the MLH1 gene is mutated in cancer cells, the uncontrolled activity of EXO1 and FAN1 makes the genome (the entire set of DNA in a cell) unstable.
Dr Antonio Porro and his team will study how MLH1 interacts with these other proteins and discover how these proteins help cancers grow. The researchers then plan to develop molecules that block these interactions, stopping cancer in its tracks and making tumours more responsive to immunotherapy.
The funding from Worldwide Cancer Research gives me the chance to pursue a novel and innovative idea that builds upon a well-established link between DNA repair pathways and immune-therapy.Dr Antonio Porro
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