2018 Invest in Research Winners

Dr. Brian Wilson
Photodynamic Therapy to Treat Melanoma

Dr. Brian WilsonMelanoma is an aggressive cancer with high mortality and morbidity rates. It is most prevalent in the skin (cutaneous), with more than 230,000 new cases and 55,000 deaths per year worldwide. The main treatment is surgery, but the disease metastasizes in 30% of patients and thereafter is very difficult to control, demonstrating a significant unmet clinical need.
Dr. Wilson aims to develop a new type of therapy for melanoma patients. In his proposal he wants to use photodynamic therapy (PDT) to treat melanoma cancer that has metastasized.

Photodynamic therapy (PDT) uses light-activated photosensitizers and currently has high success rates and excellent cosmetic outcomes in non-melanoma skin cancers. However, it has not worked for melanoma because the light doesn’t fully pass through the highly pigmented tissue. Dr. Wilson recently used a mouse melanoma model to demonstrate that applying a non-toxic “optical clearing” agent to the tumour briefly alters light scattering and allows for light to penetrate. In preliminary experiments, this resulted in complete responses to PDT.

In parallel and separately funded efforts, he is also investigating optical clearing agents to improve PDT responses in non-melanoma skin tumours in patients. This is in collaboration with a major PDT reference center in Brazil and South America. This trial is fundamental from the safety point of view to show that the optical clearing agent does not interfere negatively with PDT.

A second goal for this project is to use PDT to stimulate and enhance immune response in patients. According to animal models and patients, PDT also stimulates the immune system and leads to the destruction of untreated tumour cells, reducing or preventing tumour progression and metastasis. By contrast, surgery can reduce the immune system function in the post-operative period and increase metastatic spread. Dr. Wilson will investigate the primary tumour responses and metastatic spread of melanoma in a mouse model, treating the tumour by PDT or by surgery or by a combination of both.

Dr. Steven Chan
Repurposing Metformin and Doxycycline to Prevent Blood Cancers and Cardiovascular Disease

Dr. Steven ChanAcute Myeloid Leukemia (AML) is an aggressive blood cancer that kills more than 1,000 patients every year in Canada. Most AML patients are not cured with current therapies and die within months of diagnosis. Recent research shows that the disease actually begins to form many years before patients receive a diagnosis. This pre-leukemia condition, Clonal Hematopoiesis of Indeterminate Potential (CHIP), develops due to mutations in a special type of blood cell known as hematopoietic stem cells (HSCs).

People with CHIP are more likely to develop AML. Interestingly, they are also more likely to have heart attacks due to higher levels of inflammation in their blood cells. These discoveries raise the important question of whether treatments can be given to those with CHIP to prevent two devastating illnesses: AML and heart attacks. Given that these illnesses are life-threatening, prevention can make a huge impact on people’s lives.

Dr. Chan unexpectedly discovered that some medications commonly used to treat acne and diabetes increase the level of a protein called TET2. Mutations that reduce the level of this protein in patients with Acute Myeloid Leukemia give rise to CHIP. Thus, drugs that increase the level of TET2 protein may reduce the harmful effects of CHIP mutations. Dr. Chan wants to test this idea in a mouse model of CHIP.

Doxycycline is an antibiotic used to treat a variety of infections as well as acne, and metformin is a medication used to treat diabetes. Both medications are inexpensive, safe, and can be given to patients for long periods of time without significant side effects. If our studies are successful, Dr. Chan and his colleagues plan to start a clinical trial led by Princess Margaret Cancer Centre to determine if these drugs will prevent leukemia and heart attacks in patients with CHIP.