Targeting the complement system to improve radiation response

Our lab tries to understand how cancers exploit part of our immune system to their advantage. Our most recent work has focused on, the complement system, a part of the immune system that is best known for its role in helping fight infections. We have become very interested in this part of the immune system since cancer cells seem to hijack it for their own survival advantage. We are exploring the idea that cancer cells may be particularly dependent on these hijacked functions when exposed to external sources of damage, such as those used to kill the tumour during treatment. Our work indeed suggests that if we block certain parts of this system (with drugs) we may be able to make the cancer cell more likely to die following radiotherapy. Intriguingly, blocking certain parts of this system may also reduce the toxic effects of radiation in healthy gut. These findings therefore suggest that a drug against this system could reduce the side effects of radiation while also improving the effectiveness of radiotherapy on the tumour. We work to understand the details of how this works. The ultimate goal of these studies is to be able to use drugs against this system to improve radiotherapy in patients.

Our lab studies how tumours exploit innate immune pathways to their advantage, using a combination of cancer patient data, in vitro experiments and in vivo models. We are particularly interested in how we can use these mechanistic insights to improve radiotherapy. Our most recent work has focused on the complement system, a central innate immunity pathway which we have found is frequently dysregulated in human cancers with poor prognoses. Importantly, our work suggests that, in response to radiotherapy, cancer cells may be particularly dependent on the functions of dysregulated complement for their survival. Indeed, pharmacological inhibition of certain members of the system can enhance the effects of radiation on the tumour. Intriguingly, our work also indicates that blocking certain members of the complement system can reduce side effects from radiotherapy. We are actively investigating the mechanisms underlying these beneficial effects. The ultimate goal of our research is to identify pharmacological targets that can improve the therapeutic index of radiotherapy and ultimately improve patient’s quality of life.