Meet Steven Chan @PMResearch

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Discussing mind-preparedness and motivations for research breakthroughs.
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Dr. Steven Chan is a Senior Scientist and a Staff Physician at the Princess Margaret Cancer Centre. He is also the 2022 recipient of the Canadian Hematology Society Early Career Award.

Fortune favours a prepared mind

Imagine you found a gene that can be targeted to treat a specific type of disease. Shortly, you discover that a pharmaceutical company developed a drug for the disease that works on the same gene you found. Can you connect these two events together to guide your next step of research, and possibly make a breakthrough discovery?

This is exactly what happened to Dr. Steven Chan during his postdoctoral research at Stanford University. The disease that he was studying was acute myeloid leukemia (AML), and his focus was on a form of the disease that has a mutation in a gene known as IDH, which codes for the isocitrate dehydrogenase protein. At that time, the mutation was newly identified and there was no targeted treatment for this form of AML. To overcome this challenge, he performed a genetic screen to search other genes that when inactivated, led to the death of AML cells with IDH mutations. Soon, a gene called BCL2 caught his eyes—it codes for a protein that helps AML cells survive, and AML cells with IDH mutations appear to be highly dependent on it. Therefore, he hypothesized that inhibiting BCL2 might be a way to target this form of AML.

Coincidentally, a scientific paper came out in 2014 that described a drug called ABT199 that can inhibit BCL2. At that time, the pharmaceutical company AbbVie was investigating its efficacy in other types of cancer. Steven found this interesting—suddenly there was a very specific drug that can inhibit the target that he found. He tested the drug on AML cells with and without the IDH mutation to compare the effects. After years of laboratory experiments, it turned out that cells carrying the mutation were indeed more sensitive to the drug, while those without the mutation were less sensitive. This discovery led to a major publication in Nature Medicine, and more importantly, identified a specific patient subgroup that could benefit from this drug.

ABT199 is now known as venetoclax. It was approved by the U.S. Food and Drug Administration in 2016 and became a game changer in current leukemia treatment. Looking back, Steven is amazed at how the timing worked out—enabling him to leverage new findings that unlocked the clinical potential of his discoveries. “While luck does play a part in science, I do think that if your mind is prepared, you are more likely to connect the dots and make unexpected discoveries when these fortunate coincidences happen,” says Steven.

Gratification and gratitude are the everlasting fuels

While Steven was working on a BCL2 inhibitor, another group of scientists, led by Dr. Tak Mak, who is also a Senior Scientist at Princess Margaret, developed the first set of IDH inhibitors. Dr. Chan realized that if both therapies target IDH-mutated cells, they might work even better when combined. Using experimental models, his lab found that the combination of the two inhibitors was indeed more effective at killing IDH-mutated AML cells than each drug alone. Given the promising preclinical results, Dr. Chan launched a clinical trial in November 2020 to test the drug combination in patients.

“Getting the clinical trial started was a lot more challenging than I thought it would be,” says Steven, “but it’s all worth it when you see patients benefiting from it.”

Steven found it immensely gratifying to be a part of a journey where research discoveries were translated to the clinic. It has been the proudest moment of his career thus far and is one of his strongest motivations to continue doing bench science experiments. “My role in this journey was to make the connection between the mutation and the drugs. It has been inspiring for me to witness the drug go from being tested in cell lines, to helping patients.”

Another key motivator for Steven is working alongside people he looks up to. Steven had great admiration for his postdoctoral mentor, Dr. Ravi Majeti at Stanford University, whose vision and energy inspired Steven to pursue a career in research and academic medicine. When Steven was ready to become an independent researcher, he decided to return to Toronto. “The quality of cancer research at Princess Margaret, especially in the leukemia field, is among the best in the world.”

“Scientists at every stage of their career need mentors to help them progress. From my undergraduate to postdoc studies, my mentors played a big role in guiding me in the right direction. Even after I transitioned to an independent researcher at Princess Margaret, I have been fortunate to have the support of many mentors including Drs. John Dick, Aaron Schimmer and Mark Minden, for which I am very grateful throughout the seven years that I’ve been here.”

In December 2022, Steven received the Early Career Award from the Canadian Hematology Society in recognition of his contributions to the field of leukemia research.

Steven Chan (L) receiving the Canadian Hematology Society Early Career Award from Dr. Jason Berman (R), the Chief Executive Officer and Scientific Director of the CHEO Research Institute and the Vice-President of Research at CHEO (Children’s Hospital of Eastern Ontario). Photo credit: Penny Waddington

Beyond Cancer Research

Steven spends around a quarter of his time treating patients, while the rest of his time is devoted to research. Having his feet in both worlds, he finds good time management is a necessity. “One can be easily overwhelmed by a large number of items on the to-do list,” says Steven. “Before my day begins, I pick one or two tasks to focus on for the day. It helps me focus and also reduces my stress.”

Outside of work, he enjoys family life and spending time with his two daughters. He is very proud that one of his daughters is taking an interest in science—she picked artificial intelligence (AI) for her science fair project two years in a row. Steven himself also wonders how AI will change the world. “There are already AI applications that may soon change how medicine is practiced. I think when my daughters grow up, they will be in a world where AI is everywhere. I hope they will position themselves in a good place as the technology evolves, whether it’s in medicine or in other fields.”

Dr. Chan has received research funding from Servier Laboratories, AbbVie and Celgene/Bristol Myers Squibb. Dr. Chan has received honorarium for consulting work with Jazz Pharmaceuticals, Agios and Celgene/Bristol Myers Squibb.

Meet PMResearch is a monthly column 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.