November 28, 2023
In the middle of downtown Toronto, surrounded by major universities and hospitals, the Ontario Institute for Cancer Research (OICR) is working to better understand tumor biology and improve cancer care.
“Our goal is to bring a large community of researchers together to solve large, intractable problems in cancer, and drive new areas of oncology to stay at the cutting edge,” says Laszlo Radvanyi, PhD, OICR’s president and scientific director. “We are a unique institute that is designed to be a hub, a facilitator, that brings researchers, clinicians, and institutes all across Ontario together to solve the cancer problem.”
Precision medicine is the key. Radvanyi and his team understand that every patient’s cancer is unique, and to treat each person effectively, they must identify the genetic variations that drive their disease and tailor treatments in response.
“Our goal is to be highly translational,” says Radvanyi. “We want to pick the discoveries and innovations we believe can move into the clinic and can also lead to a new generation of products. We intersect these efforts by also facilitating the application of these innovations by new startup biotech companies in Ontario.”
Discovery and clinical care
Bernard Lam, PhD, is associate director of OICR’s Translational Genomics Lab, which features a fully equipped genomic sequencing facility, including two recently acquired high-capacity NovaSeq X Plus Systems representing the latest in next-generation sequencing technology. The lab is different from most fundamental discovery facilities because it also offers assays to support patient care through clinical trials.
“We have a clear goal of generating clinically relevant data that can be used in basic research or to inform individualized medicines for patients,” says Lam, whose lab works with several institutions across Ontario. “Our common goal is to get this done in a timely manner at the highest possible quality. We have clinical assays that can be reported back within a few weeks. Patients are waiting for a decision, and we can provide information to help guide their treatment.”
Just across the street from OICR, clinicians at one of OICR’s partner organizations, Princess Margaret Cancer Centre (PMCC), are urgently looking for new ways to help their patients. Stephanie Lheureux, MD, PhD, is a clinical investigator at PMCC who focuses on gynecologic malignancies. Lheureux relies on OICR for whole-genome and transcriptome data to guide treatment and/or monitor disease progression as part of clinical trials.
“Now we can go deeper, to the molecular level, and really differentiate subgroups of ovarian cancer that we treat differently,” says Lheureux, “and we’re doing the same investigations with uterine and cervical cancers. This changes how we practice and how we treat patients, because the different subtypes of each cancer do not respond the same ways to standard treatments.”
Lheureux is also part of PMCC’s drug development program, which leverages clinical trials to find options beyond standard chemotherapy. Genomic profiling provides a crucial layer of information, identifying variations that spur cell growth or drug resistance.
“OICR is a great collaborator,” Lheureux says. “As we do clinical trials, we often try to understand why patients may respond, or not, to a treatment. Sometimes we don’t know how a specific patient will respond; we have no clinical information to guide us. Having access to genomic sequencing gives us another tool that could give us new insights into why a patient might benefit from a treatment.”
The need for speed
Genomic information can be useful for clinical care—but only if it arrives quickly. Cancer does not wait. “Molecular profiling can provide additional information, but if the results take too long, that may not be helpful,” Lheureux says. “We need these results in a timely fashion to really guide treatment.”
Fortunately, current Illumina sequencers are fast. Ten years ago, HiSeq took several days to deliver results. Early NovaSeq Systems trimmed that to 48 hours. NovaSeq X Plus takes around 24 hours.
“You can literally come back the next day and your data is ready,” says Lam. “Having two NovaSeq X Pluses in the lab is quite amazing because it’s equivalent to six NovaSeq 6000s. Those capabilities are having an immediate impact on our sequencing capacity.”
These added capabilities could change the economics of genomic sequencing. Often, labs choose to do targeted sequencing. While this approach saves money, it could also leave out important information, such as noncoding regions that may still influence cancer. Less expensive next-generation sequencing could open a whole realm of applications.
“I think we are getting to a time where fully sequencing the whole tumor genome can be used as a companion diagnostic for every patient,” says Lam.
Lam is excited about other features, such as NovaSeq X’s increased capacity and larger flow cells, particularly for population studies. OICR is part of the Marathon of Hope Cancer Centres Network and will sequence thousands of patient genomes. That data will be combined with other biomarkers and clinical data to drive new decision-making algorithms that could better select therapies.
“There are so many things we can use genomics to study,” says Lam. “We also have projects where patients have inherited genes that drive cancer development, and we can use genomics to help monitor them throughout their lifetime, developing early cancer detection tools so we can catch these tumors fast and intercede. We are getting to the point where every single person in the community can benefit.”
