November 13, 2019

Winning presentation points to more personalized medicine at OMPRN Pathology Matters meeting

OICR and OMPRN leaders pose for a photo with students and fellows who presented at the fourth annual Pathology Matters meeting in Ottawa.

Dr. Brian Keller, an Anatomical Pathology Resident from Ottawa, was one of those recognized for outstanding presentations and innovative research at this year’s Pathology Matters meeting

Through his years of research training, Dr. Brian Keller developed expertise in culturing cancer cells. Under precise conditions in a controlled lab environment, he could take a part of a patient’s tumour and grow it into an experimental model for further research. Keller would study these models to find new treatments for future cancer patients, but he wondered if these models could also help patients today.

While he was an MD/PhD trainee, he received a patient’s sample that was unique. It defied the typical behaviour of a sample and grew remarkably well, faster than normal, exhibiting the cancerous traits that could make it an excellent experimental model.

The sample came from a patient with advanced melanoma whose disease had returned after multiple rounds of treatment. Keller recognized the opportunity to help.

Dr. Brian Keller

“This patient was in a very difficult situation,” says Keller, who is now an Anatomical Pathology Resident at The Ottawa Hospital. “The standard treatments weren’t working and the patient’s oncologist was thinking of second- and third-line treatment options. Knowing that we had this model in the lab, we thought that we could potentially find a better treatment option if we looked at hundreds of available drugs.”

Keller mobilized the patient’s healthcare team around his idea to find new possible treatment options for the patient. He worked with the patient’s pathologist, medical oncologist, molecular geneticist, laboratory and research technicians, and several other graduate students to grow the tumour sample, analyze its DNA and test approximately 1,200 available drugs on it. Their results aligned with the oncologist’s clinical decision and the patient had an impressive response to treatment, Keller says.

“Every cancer is unique and we’re working towards getting the right treatments to the right patients at the right time,” says Keller. “This represents the direction in which our field is moving. I am hopeful that our generation of clinicians and healthcare providers can help bring more personalized and effective treatment to our patients.”

Keller went on to characterize the patient’s disease and found that it had a unique mutation in the BRAF gene that had never been modeled before. This novel experimental model will continue to serve as a research tool in Dr. John Bell’s lab at the Ottawa Hospital Research Institute, where Keller performed his research, and throughout the global scientific community. The team has made the model available through the American Type Culture Collection’s general repository and a manuscript of the case is under preparation.

“I am fortunate to have had the opportunity to train in Dr. Bell’s lab, where exploration and collaboration are strongly encouraged,” Keller says. “Without exploration, we cannot make discoveries, and without collaboration, we cannot bring our discoveries to our patients.”

Keller presented his findings at the fourth annual Pathology Matters meeting in early October, hosted by the Ontario Molecular Pathology Research Network (OMPRN). His story won him an Outstanding Presentation Award. Other presentation award recipients included:

  • Dr. Lina Chen, Anatomical Pathology Resident, Queen’s University
  • Christina Ferrone, PhD Candidate, Pathology and Molecular Medicine, Queen’s University
  • Chelsea Jackson, PhD Candidate, Pathology and Molecular Medicine, Queen’s University

OICR would like to congratulate award recipients and thank the organizing committee for a successful meeting.

Learn more about the OMPRN

August 12, 2019

Dr. Rola Saleeb on her path to becoming a pathologist

Rola Saleeb
Dr. Rola Saleeb, Assistant Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto.

OMPRN grantee and former Transformative Pathology Fellow discusses her recently-awarded faculty appointment with the University of Toronto

Despite research advances in identifying the subtypes of kidney cancer, treatment decisions are often based on the size of a patient’s tumour. Dr. Rola Saleeb, who has been studying kidney cancer for nearly a decade, thinks there’s a better way to make these decisions.

“Each month, more than 500 people are diagnosed with kidney cancer in Canada,” says Saleeb. “These individuals and their oncologists face tough decisions to make about their treatment options and I want to help make that decision easier.”

Saleeb, a former OICR Transformative Pathology Fellow and two-time Ontario Molecular Pathology Network (OMPRN) grantee, has recently become a certified pathologist and faculty member in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.

Throughout her doctoral research, Saleeb developed a classification system that could help pathologists distinguish between aggressive kidney cancers and less aggressive cancers. She says this system could, one day, help spare patients from unnecessary surgery if they don’t have aggressive tumours. Additionally, she says classifying these tumours could enable the development of new therapies for these subtypes.

Now as a certified pathologist, Saleeb is the second Transformative Pathology Fellow to have been recruited to a faculty position. Both former fellows have committed to a career where research and development is central to their practice of pathology.

“Not all pathologists do research,” says Saleeb. “But for me, I feel like I can help more patients if I can help find solutions to unsolved problems.”

Saleeb is currently completing a validation study on her classification system. She looks forward to implementing the system at St. Michael’s Hospital and broadening her research to study the molecular origins of kidney cancers and new kidney cancer prevention strategies.

Read more about OMPRN here or find current pathology funding opportunities here.

June 26, 2019

Patterns in pancreatic cancer samples lead to better prognostic power

Dr. Sangeetha Kalimuthu, gastrointestinal pathologist at the University Health Network, works in her lab.
Dr. Sangeetha N Kalimuthu, gastrointestinal pathologist at the University Health Network, works in her lab. (Photo: UHN)

University Health Network pathologist teams up with OICR researchers to develop an improved pancreatic cancer classification test that can better predict the severity of the disease

Under a microscope, pancreatic cancer often looks like a haphazard collection of cells with various shapes and sizes, but Dr. Sangeetha N Kalimuthu saw something different.

She had been analyzing hundreds of pancreas resections, which are classified using the current three-tiered staging system – well, moderate and poor – but found that the vast majority of cases fell into the moderate category, offering little information to physicians about how best to treat these patients.

N Kalimuthu, a gastrointestinal pathologist at the University Health Network (UHN), noticed that certain patterns in cell shape matched the molecular profile of tumours with poorer survival for patients. She teamed up with Drs. Runjan Chetty and Steven Gallinger at UHN to see if what she noticed was true. Gallinger is Director of OICR’s PanCuRx Translational Research Initiative.

In a study recently published in Gut BMJ, the study group assessed more than 800 pancreatic ductal adenocarcinoma (PDAC) slides and developed an improved classification method that could help differentiate patients with the most aggressive tumours.

“Our aim was to revise and reappraise the current grading system to find features that correlated with these molecular subtypes,” says N Kalimuthu. 

By linking molecular profiles of tumours with their appearance, N Kalimuthu was able to develop a classification method that can be easily integrated into current pathology laboratories.

“Any pathologist in any part of the world can do this,” says N Kalimuthu. “It’s the bread and butter of what pathologists do. It’s fast, cheap and accessible.”

N Kalimuthu also says that this method can be augmented using deep learning methods to reduce turn-around times and variability from one pathology laboratory to another.

“Pathologists have had a long, rich history in their vital roles to diagnose and stage pancreas cancer,” says Gallinger, who is co-author of the publication. “This study is an elegant demonstration of the potential of personalized medicine, with the promise of improved outcomes for our patients.”

Read the full UHN News story here.