A leader in early therapeutics development
Dr. Lillian Siu was inspired to become an oncologist in her teenage years. After her mother was diagnosed with breast cancer, she accompanied her to hospital visits for twelve years, receiving chemotherapy at Princess Margaret Cancer Centre (PM).
“I felt very comfortable in the environment and it started to feel like home. Then I knew it was my calling to study cancer,” says Lillian, who went on to complete a Doctor of Medicine degree in 1991 and a medical oncology residency in 1995, both at the University of Toronto.
Today, Lillian is a global leader in drug development, and through her long career, she has seen life-changing advances that have revolutionized patient care.
She is also the first Canadian to be named President-Elect for the American Association for Cancer Research – the largest cancer research organization dedicated to accelerating the conquest of cancer.
“It is both daunting and exciting,” says Lillian of this prestigious global role. “I’m excited to learn different aspects of cancer research and foster collaboration with other cancer centres. I think in a world where disparity is a definite issue, it will allow us to break some barriers, ensuring that advancements and resources are accessible.”
Lillian has dedicated her life’s work to early drug development.
When she started her career, there were only chemotherapy drugs. “There was no immunotherapy or antibody drug conjugates. It was at the dawn of the molecular era that empowered drug discoveries.”
Formal training for early phase cancer drug development was only available in a few centres in the world. San Antonio, Texas, one of the hubs with extensive pharmaceutical collaborations, attracted early drug developers to the field.
Lillian wanted to apply for a fellowship there, but the spots had been filled and she needed to wait for another year. Instead of simply waiting around, she sought out to create a similar training experience for herself, despite the absence of such a program.
“I asked my supervisor Dr. Malcolm Moore at that time: ‘I want to go to San Antonio in a year. Can I do a fellowship with you similar to that?’ I was fascinated to learn more about early drug development, and I wanted to be prepared for San Antonio. This would allow me to understand more about early phase trials.”
Lillian completed an oncopharmacology fellowship at PM, before heading south for San Antonio, where she encountered one of the first early drug development studies of EGFR inhibitors and trained with many vanguards of the field. She came back in 1998 and after three years, she became the Director of the Phase I Program and co-Director of the Drug Development Program at PM. Her efforts have brought the two programs to a much larger scale, training over 70 people in the world who aspired to become drug developers and clinical trialists.
“The message is that it's okay to create a new path,” says Lillian, proud of the fact that she was able to be an innovator, “I've always wanted to be the one that can go far by having original ideas.”
A catalyst for cancer research innovations
“Bringing various expertise together allows us to transform original thinking into actions.” Lillian identifies her role as close to being a catalyst, accelerating translational research by finding different dry lab and wet lab collaborators to work together.
One of the pinnacle examples is the INSPIRE study (NCT02644369), a highly impactful clinical trial that studied the effects of the immunotherapy, pembrolizumab, in patients with advanced solid tumours.
This flagship phase II study was led by Dr. Lillian Siu and Dr. Pamela Ohashi at PM. The two investigators, who are respectively renowned for clinical drug development and T-cell immunology research, were tasked to bring basic, translational, and clinical immunology together. They established the Tumor Immunotherapy Program (TIP) at PM that conducted the study and many more immunotherapy trials.
The INSPIRE study started in 2016, enrolling 106 patients with advanced solid tumours spanning a variety of tumour types including head and neck cancer, breast cancer, ovarian cancer, melanoma, and mixed-type cancer. The team secured pembrolizumab, an immune checkpoint inhibitor from Merck, the pharmaceutical company, to treat patients and evaluate gene changes and immune biomarkers in tumor and in blood in response to the treatment.
One of the key discoveries from INSPIRE published in Nature Cancer showed that early and routine circulating tumour DNA (ctDNA) testing can be used to monitor response to prembrolizumab, providing important evidence for the development and application of liquid biopsy. It has also contributed the most relevant data that led to the funding approval by Medicare for ctDNA monitoring for cancer patients receiving immunotherapy in the U.S.
INSPIRE sets up a ‘gold standard’ for investigator-initiated therapeutic studies. Multiple publications have emerged from data generated from the study. Another achievement from INSPIRE, reported by two co-lead authors Dr. Eric Zhao and Dr. Enrique Sanz-Garcia, showed that methylation and fragmentation status of cell-free DNA in patient plasma samples can predict patient survival (published in Cancer Discovery in 2024). This technique can estimate ctDNA levels without the need to access tumour tissues, which makes it very adaptable for clinical settings.
In addition to these outputs and in collaboration with Dr. Trevor Pugh, the team is currently looking at the T-cell receptors (TCR), collected from patients’ biological samples before and during their treatment. “We hope to understand what changes in the TCR repertoire can predict patients’ response to the therapy, what are the signs to tell which patients will have better outcomes, and how their TCR diversity varies in the blood and the tumour,” says Lillian.
“What’s more important than each discovery is the multidisciplinary thinking fostered by the collaboration. The scientific and clinical teams work together to have mutually beneficial crosstalk, which elevates the discovery to a higher level,” says Lillian.
Building on top of the established collaborations and the discoveries of the INSPIRE study, Lillian initiated the NIP-IT! Program, which includes four clinical studies since its inception, each targeted at a different type of tumour, to intercept and intervene in cancer relapse based on the ctDNA levels in the blood. NIP-IT! provides a platform to include future interception studies in other tumour types. As the name suggests, the ultimate goal of NIP-IT! is to nip cancer in the bud.
Today, Lillian holds many important positions at PM. Not only does she have both clinical and research appointments as a Senior Medical Oncologist and Senior Scientist, but she is also the Director of the Phase I Clinical Trials Program, Co-Director of the Bras and Family Drug Development Program, Clinical Lead for the Tumor Immunotherapy Program and BMO Chair in Precision Genomics at PM.
Lillian enjoys working in a multidisciplinary group. Over the years, collaborating with multiple academic and pharmaceutical teams has earned her high esteem within the international oncology community. She has served on the Board of Directors for the American Society for Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR).
A multitasker with tenacious professionalism
Juggling multiple programs and holding many important roles, Lillian has evolved into an expert multitasker: “I try my best to manage multiple tasks at the same time while keeping my standard to do a decent job." Whether it's managing online meetings, emails, or updating medical records, efficiency is key in her fast-paced world.
"At the end of every day, I make sure I've closed all the loops," she emphasizes showing tenacity and commitment.
"To promise something and not deliver is not in my code of professionalism," she asserts, “because that means I have no way to judge my skills and no way to predict my time.”
On female leadership, Lillian encourages women not to focus on how they are underserved, but to show others what they can do.
“I don't want to ignore the fact that there is a disparity, that there are fewer female researchers or leaders in high positions.”
“But I've never been threatened by that. I never feel that I cannot speak up in a panel of men. And I never feel that their science is better than my science if I consider myself on equal footing.”
“How do you prove to somebody that you're not threatened by it? You do better. It is more important for me to demonstrate what I can do than to promise you what I can do.”
Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.