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Top team of multidisciplinary experts will tackle unmet clinical needs for patients diagnosed with rare neuroendocrine tumours

Sunnybrook Research Institute scientist Dr. Hon Leong says celebrities like Steve Jobs and Aretha Franklin, both diagnosed with rare neuroendocrine tumours, would have been among those to benefit from work he and his incredible team of experts are expanding upon with new funding awarded through a 2023 Terry Fox New Frontiers Program Project Grant.

“We have developed a truly world-class research team that is focused on coming up with new clinical tools and therapies with transformative potential for patients diagnosed with these tumours,” says Dr. Leong, the new program’s co-leader alongside Dr. Benjamin Lok. “I think knowing that TFRI is taking each step with us in this journey, we are embodying exactly what Terry Fox wants us to do, which is to work with everyone possible to make a difference.” 

Their funding and work will help to address what is currently an unmet need for these patients. Neuroendocrine tumours are often diagnosed late and current treatment options are poor. Moreover, the incidence rate is growing and our understanding of this disease needs improvement. Dr. Leong’s team hopes their multidisciplinary, pan-Canadian team will be able to shift the tide with developments like a blood test for the early detection of these rare tumours, found in parts of the body such as the pancreas and lungs.

This program will receive $2.4 million over four years (2023-2027) to combine new technologies to improve understanding of NETs, and create better diagnostic tools and novel, patient-centred treatments. The team’s connection with Sunnybrook Health Sciences Centre’s NET clinic, which sees most NET patients in Ontario, will create a significant advantage through accessibility to tumour samples and monitoring of patients on trials.

The neuroendocrine system is made up of nerves and gland cells located throughout the body. Together these cells control the production and release of hormones that regulate several body functions, including breathing and digestion. If a tumour starts in these cells – whether in the gastrointestinal tract, lungs, pancreas, or elsewhere – it can grow and destroy neighbouring tissue and spread to other parts of the body. These types of cancer can be extremely aggressive and, unfortunately, resistant to most treatments.

The program comprises several projects with specific aims and goals to help address the current unmet clinical needs:

  • To improve our understanding of these deadly tumours and identify new treatment avenues by diving into the role of a signalling pathway known as miR-181 in three major types of NETs: pancreatic NETs (PanNETs), therapy-induced neuroendocrine prostate cancer (NEPC) and small cell lung carcinoma (SCLC).

  • To focus on understanding and, if possible, delaying or preventing NEPC, which typically results in death within two years of diagnosis. This project centres on studying the role of circular RNA in driving the transformation of this cancer and understanding how this transformation results in resistance to advanced androgen-receptor targeting therapies. The team aims to gauge the effectiveness of targeted therapy and immunotherapy, as current treatments are limited and often ineffective.

  • To advance therapeutic strategies in neuroendocrine carcinoma (NEC), a rare and aggressive form of cancer that occurs when cancerous neuroendocrine cells spread to other parts of the body. A preclinical “basket” study is proposed to efficiently explore therapeutic vulnerabilities that are common across NECs, regardless of their original site in the body.

  • To improve diagnostic pathways and patient monitoring using an innovative approach called “liquid biopsies.” Essentially a blood test, a liquid biopsy could improve diagnosis, monitor disease progression and help predict patient prognosis in oncology. First, they will develop a “universal NET liquid biopsy” to detect any neuroendocrine tumour followed by individual liquid biopsies for specific types of NETs (PanNETs, SCLC, and NEPC).

  • The team will use advanced techniques such as specialized animal models and microfluidics to test the effectiveness of various therapeutic approaches and thus test a wide variety of therapies and tumours regardless of disease site or stage. The bioinformatics group will ensure data standardization, enabling confident data sharing and collaboration.
“In our minds, this is probably the most prestigious cancer research grant in the world.  When you first apply for this award, a sense of true responsibility surrounds the application and it gives us more meaning,” says Dr. Leong, a translational urology researcher and associate professor at the University of Toronto. “We are filled with deep admiration [for Terry Fox] and a desire to do the most with the funding.”