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“Dream team” science helps move Ontario ahead of the curve on hard-to-treat cancers
OICR’s Translational Research Initiatives (TRIs) made a lasting impact for patients.

OICR’s Translational Research Initiatives (TRIs) made a lasting impact for patients.

In 2017, ovarian cancer research was due for a new approach.

Despite the best efforts of scientists, clinicians and patients, outcomes hadn’t improved for almost 50 years, and the disease always seemed one step ahead.

Gaining ground on ovarian cancer was going take something bold. It was going to take teams of experts asking questions that matter to cancer patients and working together to answer them.

And that’s exactly what OICR had in mind when it created the Ovarian Cancer Translational Research Initiative (TRI) that same year, part of a $24 million investment by the Government of Ontario to support research teams to tackle some of the most challenging cancers.

The OICR TRI program united clinicians and scientists into five teams with clear goals and deliverables. Four teams were charged with delivering solutions for a specific cancer (ovarian, brain, pancreatic and leukemia) while the fifth TRI was created to harness immuno-oncology to treat cancers.

Although the TRI program came to an end in 2022, its legacy lives on in innovative discoveries that are helping give cancer patients a brighter future.

In the Ovarian Cancer TRI, this includes making major discoveries about ovarian cancer and how to treat it, launching two start-up companies, and touching the lives of more than 700 patients who participated in nine new clinical trials.

“The TRI brought together a ‘dream team’ of clinicians and scientists and allowed us to be bold and take risks,” says Dr. Amit Oza of the University Health Network (UHN), who co-led the Ovarian Cancer TRI alongside UHN’s Dr. Robert Rottapel. “OICR funding helped us to better understand how ovarian cancer cells change and become resistant to treatment, and that helped us get ahead of ovarian cancer after seemingly trailing behind.”

Unique teams that reach across disciplines

OICR has a long history of bringing together experts from across Ontario and around the world to solve the biggest challenges in cancer. But the TRIs took OICR’s collaborative, impact-driven approach to the next level.

The program provided significant, multi-year support that reached across institutions and disciplines. It gave research teams a clear, singular goal but also the leeway to approach it from different angles. It also leveraged areas where Ontario had proven strengths – like immune-oncology, stem cells, genomics and clinical trials – in the hopes of translating innovations into patient impact.

“OICR invested in TRI’s in order to support Ontario’s international leaders in accelerating transformative innovations,” says Dr. Teresa Petrocelli, Director Clinical Translation at OICR. “The TRIs fostered partnerships amongst those experts, providing them with support and resources so that they could address key clinical priorities in a coordinated way, translating them for positive patient impact.”

The TRIs were led by some of the top talent in Ontario cancer research. In addition to Oza and Rottapel (ovarian cancer), other teams were led by Dr. Peter Dirks and Dr. Michael Taylor (brain cancer), Dr. John Bell and Dr. Marcus Butler (immuno-oncoloy), Dr. Steve Gallinger (pancreatic cancer) and Dr. John Dick and Dr. Aaron Schimmer (acute leukemia).

For acute leukemia, the TRI program came at just the right time. OICR was already at the forefront of leukemia research, thanks in part to Dick’s discoveries about the stem cells that drive leukemia relapse. But relapse was still common, and the standard treatment – a heavy dose of chemotherapy – caused severe side effects. The Acute Leukemia TRI allowed Dick and Schimmer to recruit a multidisciplinary team to try and turn knowledge about leukemia stem cells into innovative solutions for patients.

“We were able to gather people together who might not have otherwise been studying leukemia stem cells, and raise the caliber of everyone’s work,” Schimmer says.

Wide-ranging innovations

During the term of the TRI program, the teams made significant progress in the five priority areas.

For the Ovarian Cancer TRI, much of this progress revolves around an ambitious prospective trial called BioDIVA. The study recruited more than 500 women with high-grade serous ovarian cancer, the deadliest form of disease and most likely to relapse. The tumour samples from BioDIVA – collected at diagnosis, during treatment, and at relapse – continue to be an invaluable resource for understanding why ovarian cancer recurs.

Other Ovarian Cancer TRI studies have looked more directly at treatment options for ovarian cancer, and ways to overcome resistance to treatment. In a clinical trial involving 100 women, Oza and UHN Clinician Scientist Dr. Stéphanie Lheureux found that a unique combination of medicines could extend the lives of women whose ovarian cancer relapsed. In other drug discovery research supported by the TRI, Rottapel and Dr. Methvin Isaac identified a promising target called GCN2 that could lead to a brand new class of therapeutics for ovarian cancer.

These kinds of wide-ranging discoveries covering the entire spectrum of cancer care were typical of the diverse TRI teams.

In acute leukemia, researchers made inroads in early detection by finding signs of acute leukemia a decade before symptoms surfaced. They also developed a diagnostic test that can predict a leukemia patients’ chances of relapsing after treatment. And discoveries about the role of fat production in the development of leukemia stem cells could help create therapies that stop relapse before it happens.

Other key innovations from the TRI programs include using genome sequencing to personalize treatment for pancreatic cancer, overcoming resistance to immunotherapy in triple-negative breast cancer and paving the way for a new class of therapeutics for brain tumours.

“Our groups made fundamental discoveries that translated into the clinic and are having lasting clinical impacts,” says Schimmer.

Long-lasting impacts for patients

Though the TRIs have officially ended, their influence is ongoing. In total, nearly 1,600 patients were recruited to TRI studies, and the programs generated nine different patent applications.

Some TRI-supported studies are still in progress, and other related studies were made possible by leveraging the TRIs to secure funding from other sources. The Pancreatic Cancer TRI was particularly effective at bringing genomic discoveries to patients through several innovative clinical trials, and was converted to an ongoing program under OICR’s Clinical Translation theme called PanCuRx.

The broader TRI initiative evolved into OICR’s Clinical Translation Pathway (CTP) which employs a similar approach but with even clearer pathway toward clinical impact and stronger connections across the OICR community. The CTP program prioritizes projects that are developing biomarkers, diagnostics and therapeutics and are ready to launch trials for their clinical validation – which was a challenge for some TRI-supported projects. Moreover, through the CTP program, funding is made available to support the implementation of cancer innovations into healthcare policy and clinical practice.

Through CTP, OICR continues to fund projects that grew out of the TRIs, including Dr. Mitchell Sabloff’s work testing biomarkers and treatments for acute myeloid leukemia, and Lheureux’s clinical trial using liquid biopsy to guide treatment for relapsed ovarian cancer.

“The TRIs weren’t just another award or funding stream,” Petrocelli says. “They marked an evolution in how OICR collaborates across institutes and disciplines to make the greatest difference for people affected by cancer.”