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Understanding the effects of radiation therapy on the tumour microenvironment to improve treatment efficacy

Radiotherapy has been a main pillar of cancer treatment for over a century. Even today, half of all people diagnosed with cancer receive radiation therapy at some point of their cancer journey. But despite its prevalence – and its high success rates – many questions remain as to why radiation therapy works for some patients, but not others, and how it can be more effective for more patients.

“The main reason for this gap is that we still don’t have a full picture – at the molecular level – of exactly what is happening to cells in and around the tumour after treatment,” explains Dr. Shane Harding, a scientist at the Princess Margaret Cancer Centre in Toronto specializing in DNA damage and radiation biology. “In one way, as long as radiation kills the tumour that’s really all that matters. At the same time, by studying exactly how this process works we provide an opportunity for improvement.”

Over the next three years, Dr. Harding will receive $450,000 to explore how radiation therapy affects the tumour microenvironment thanks to funding from a 2023 Terry Fox New Investigator Award. The project will specifically focus on better understanding if there are ways to make radiation therapy enhance the immune system’s response to treatment in a way that would make it favourable to combine radiation with immunotherapy to improve patient outcomes.

“Recently, we have found that radiation can activate a viral-like response in cancer cells that alters the immune system to potentially make the cancer more sensitive to immunotherapy,” explains Dr. Harding. “We think that this response can be enhanced if we use novel drugs to manipulate how cells respond to radiotherapy at the molecular level and this funding provides the support to pursue this research angle ”

To do this, Dr. Harding and his team will first use modern technologies to profile thousands of cells from prostate cancer patients before and after treatment with radiation therapy to gain unprecedented detail of the cellular response to radiotherapy. They will also use different models in their lab to test if specific drugs can be used to manipulate these responses in ways that stimulate the immune response to radiation therapy. This will ultimately allow them to test if these new drugs can be used to make treatments that combine radiotherapy and immunotherapy more efficient, improving patient outcomes.

Dr. Harding will be mentored by a TFRI-funded team of world-leading specialists in the tumour microenvironment. This collaboration will provide valuable expertise to make Dr. Harding’s experiments more powerful and help him quickly move findings to more types of cancer.

“Our team-based approach means we are poised to rapidly ask these questions in breast, cervical, brain and pancreatic cancers,” says Dr. Harding. “Ultimately, our goal is to give new molecular detail to the radiotherapy response in various cancer types and to use this information to maximize treatment success, including by increasing the number of patients who can reap the remarkable benefits of immunotherapy.”