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Testing novel nanoparticles to improve treatments for deadly liver cancer

An early-career clinician-scientist in Toronto is hoping to turn the tide on a deadly form of liver cancer with new funding from the Terry Fox Research Institute.

Liver transplant specialist and clinician-scientist Dr. Mamatha Bhat (Ajmera Transplant Centre-University Health Network and Toronto General Hospital Research Institute) will use the funds from her recent Terry Fox New Investigator Award to search for innovative ways to treat hepatocellular carcinoma (HCC), the cancer most rapidly increasing in incidence in Canada. Bhat is one of four scientists receiving the award, valued at $450,000 over three years, following a rigorous annual peer-review competition conducted by TFRI.

“As someone who sees patients with this disease in the clinic, I know how important it is to find innovative solutions for HCC,” explains Dr. Bhat. “Not only because it’s affecting more and more Canadians each year, but also because it has a dismal five-year survival rate of just 18 per cent, which is among the worst in all cancers.”

HCC is often diagnosed when it is too late for curative therapy. Only a small proportion of patients with early-stage HCC are candidates for liver transplantation or other curative therapies. A major reason why HCC is so deadly is that it often arises in the setting of cirrhosis, which causes full-fledged scarring of the liver, she says. This makes it hard for the liver to metabolize chemotherapy, reducing the efficacy of treatment while significantly increasing negative side effects.

With her New Investigator Award, Dr. Bhat will seek to address these issues by testing out a new way to treat HCC. In partnership with the Terry Fox New Frontiers Program Projects Grant (PPG) team led by Dr. Gang Zheng, Dr. Bhat will test the safety and efficacy of a novel lipoprotein-like nanoparticle created by the PPG team. This nanoparticle, known as PorphyHDL, can deliver cancer drugs or RNA interference therapy directly into cancer cells, enabling targeted therapy and limiting unwanted side effects. It is especially well suited for targeting liver cancer, due to the high expression of receptors for lipoproteins on the liver cancer cell surface.

“The goal of our study is to demonstrate that it is possible to safely use a natural fat transporter-like carrier, such as PorphyHDL, as an image-guided delivery tool (i.e. theranostic strategy) to treat patients with HCC, regardless of whether or not they have cirrhosis,” says Dr. Bhat. “This would represent a completely novel approach to treating HCC, which is urgently needed for this cancer that continues to affect a growing number of Canadians.”

The PPG team is currently working on securing Health Canada approval for use of such nanoparticles in clinical trials, which is why Dr. Bhat hopes to collect enough data using mouse models and biopsied liver tissue to move her research forward to a clinical trial.

Dr. Zheng and his group are excited to mentor and work with Dr. Bhat and her lab. “As a brilliant young hepatologist, Dr. Bhat will be able to translate our porphysome technology into clinical application by treating patients with HCC, by which time we expect our TFRI program will have commenced its first-in-human trials,” says Dr. Zheng. “Therefore, her proposed project represents a truly innovative and exciting application of our nanotechnology for a cancer dramatically rising in our country and in urgent need of curative therapy.”

Mentoring Program: Porphysome Nanoparticle Enabled Image Guided Cancer Interventions