Article by Kyla Trkulja

Graphic design by Xinyi Li

Liver cancer is one of the most difficult types of cancer to treat, making it the third most common cause of cancer death around the world.¹ The prognosis for patients diagnosed with the disease is poor, with only 35% of patients with early-stage disease surviving 5 years after diagnosis—and a mere 3-12% of patients surviving this long if the cancer spreads.¹ It is difficult to treat because many of these patients often also have liver disease, making them unable to tolerate chemotherapy or surgery.  

Dr. Mamatha Bhat, a hepatologist and clinician-scientist at Toronto General Hospital, is using creative and innovative approaches to try to improve these grim statistics and the lives of patients with liver disease. After completing her medical education and residency in internal medicine and gastroenterology at McGill University, she pursued a research fellowship and obtained her PhD in medical biophysics from the University of Toronto. She currently runs a translational research program using an interdisciplinary approach that aims to improve the outcomes of patients after liver transplantation—of which 35-40% are cancer patients. 

Dr. Bhat describes the ability to perform a transplant for those with liver cancer as a “unique paradigm,” as transplantation is not a method of treatment for other types of cancer, with the exception of cancers originating in the blood. Clinically, she looks after 350 patients who are referred for a liver transplant before, during, and after their surgery. On the research side, she aims to uncover ways to improve patient outcomes post-transplant—specifically by using nanoparticles to prevent and treat recurrence of liver cancer. 

Nanoparticles to treat liver disease and cancer were developed in collaboration with Dr. Gang Zheng at the Princess Margaret Cancer Centre. Put simply, these types of nanoparticles contain proteins and drugs that can treat the liver disease and cancer a patient may have. They bind to receptors that are specifically expressed on the liver and its cancer cells, such as the receptors used to take up cholesterol. This new and innovative approach allows the treatment to be targeted and delivered to the specific cells in need. 

“With this approach, we can very selectively target the liver cancer cells,” Dr. Bhat explains. “Beyond that, we might be able to target specific molecular profiles, and also [optimize] the dose, depending on the degree of liver dysfunction that the patient has, so this is a very unique consideration in cancer where people have underlying liver disease.” 

Dr. Bhat has demonstrated the efficacy of this treatment in animal models through her collaboration with Dr. Zheng, which has been supported by the Terry Fox Research Institute and the Canadian Liver Foundation. Dr. Zheng’s nanoparticle technology will soon be studied in a clinical trial with oncologists at the Princess Margaret Cancer Center to test this therapy in a variety of cancer types. If the trial is safe and effective, it could be brought to the clinic as a way to treat those with liver cancer and hopefully improve their disease outcomes. 

The use of nanoparticles to target and treat liver cancer is a way of overcoming one of the biggest challenges in oncology, which Dr. Bhat describes as treating cancer with a “one-size-fits-all” approach. “Everyone has their own background, their own clinical characteristics, their own disease manifestation,” she explains. “Each person is unique … but we still go based on clinical guidelines, and clinical guidelines may be good for the population as a whole, but they may not be good for individuals within that population.” By tailoring both the dose and type of treatment inside the liver-specific nanoparticle, this challenge is being addressed to make cancer treatments both safer and more effective while considering the patients’ underlying conditions such as chronic liver disease and cirrhosis. 

Dr. Bhat stressed the importance of collaboration in making this research possible, both between researchers and between research sites. “The world has become much more complicated, and it isn’t possible for one single person to have the whole skill set to address a specific problem,” she said. “It used to be that you could be one lab doing your own thing. But I think things evolved and changed over time.” She is now utilizing tools she has learned from other disciplines, such as bioinformatics and machine learning, to aid her research in personalizing treatment. 

This openness to new approaches and collaborations is described by Dr. Bhat as one of the most important characteristics to have as a researcher, as “the world has become much more interdisciplinary.” This has been exceptionally important in her role as a clinician-scientist, where broad and creative thinking are necessary to tackle an issue seen in the clinical setting. “It’s not just hard work,” she says. “It’s also working smarter.” 

Using her clinical experience to inform on her research projects is an exceptionally rewarding part of her career, despite the challenges that go along with managing the dual roles. She explains that a positive attitude, interest and passion for the work being done, and motivation to dedicate extra years to acquiring the skills necessary for both roles are essential to succeeding as a clinician-scientist. If you have the passion and openness, the role is an excellent way to tackle the gaps in healthcare since you can inform projects from your own clinical experiences. 

Using these skills, Dr. Bhat is aiming to play a role in the future of liver disease and cancer research and care, which she envisions as moving away from the one-size-fits-all approach to treatment and embracing the potential for new and innovative targeted therapies. She believes that these are key to improving outcomes for patients with liver cancer and reducing fatalities, similar to what has been done for other types of common cancer such as breast and colorectal. Nanoparticle-based therapies are one example of how this may be done, so she looks forward to bringing these from bench to bedside in the coming years.

References:

1. American Society of Clinical Oncology. (2022, February 24). Liver cancer – statistics. Cancer.Net. Retrieved May 20, 2022, from https://www.cancer.net/cancer-types/liver-cancer/statistics