May 30, 2019

Predicting the course of pancreatic cancer

Dr. Benjamin Haibe-Kains, Senior Scientist at the Princess Margaret Cancer Centre and OICR Associate poses for a photo in a data centre.
Dr. Benjamin Haibe-Kains, Senior Scientist at the Princess Margaret Cancer Centre and OICR Associate.

Meta-analysis of 1,200 patients with pancreatic cancer reveals a new way to identify those with very aggressive tumours who may benefit from alternate treatment approaches

Only half of pancreatic cancer patients who undergo standard chemotherapy and surgery live a year after their initial diagnosis. In the face of these dismal statistics, patients are faced with the challenge of deciding whether they want to proceed with treatment that may have unpleasant side effects. If clinicians could identify patients who would not benefit from standard therapies, they could help these patients make more informed treatment decisions or recommend alternative palliative treatment approaches.

As part of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx) team led by Dr. Steven Gallinger, Dr. Benjamin Haibe-Kains recognized that computational modeling can be used to help inform these decisions, but to design a robust predictive model he would need much more data than any individual study had ever collected.

Building the data foundations

Haibe-Kains, who is a Senior Scientist at the Princess Margaret Cancer Centre and OICR Associate, began his investigation with a dataset from PanCuRx – the largest collection of genomic and transcriptomic data on primary and metastatic pancreatic tumours to date. He and his lab then incorporated an additional 1,000 cases of pancreatic tumours from studies around the world that had collected both patient samples and information about how each patient responded to treatment.

“The datasets that we aggregated were a mixed bag of different types of data collected through different profiling platforms by different institutions,” says Haibe-Kains. “We took on the challenge of harmonizing the heterogeneity of these resources which nobody else had done.”

Previously, the Haibe-Kains Lab developed a computational method that could make incompatible transcriptomic data compatible. They had used this method to find four new breast cancer biomarkers to predict treatment response and they recognized that they could apply similar methods to harmonize pancreatic cancer data as well.

The dataset resulting from the harmonization is now the largest pancreatic cancer dataset, and Haibe-Kains has made it freely available for other researchers to use and study through the MetaGxPancreas package.

Making a predictive model

Haibe-Kains and his team set out to develop a computational model that could predict if a patient would survive for a year after their biopsy. They used machine learning techniques to exploit their rich dataset, find common patterns in the genomic data of aggressive tumours, and developed PCOSP – the Pancreatic Cancer Overall Survival Predictor.

“Our approach was to look at how one gene was expressed relative to another and relate that to how long a patient lived after biopsy,” says Haibe-Kains. “That may sound simple, but that means dealing with nearly 200 million pairs of genes, which is a significant amount of data to compute.”

As recently described in JCO Clinical Cancer Informatics, the group refined PCOSP using ensemble learning – the combination of several machine learning techniques to improve a model’s accuracy of predictions.

“PCOSP is actually a combination of hundreds of models and not just one,” says Haibe-Kains. “We tested about a thousand models, selected the models that could predict early death very well and combined them to make a stronger classifier.”

Using prediction to power patient decisions

Haibe-Kains says that as the infrastructure for routine sequencing progresses, PCOSP can be translated into clinical practice to help clinicians determine which patients would not benefit from standard treatment and which may benefit from alternative treatment approaches.

“Pancreatic cancer is a challenging disease but if we can predict the course of the disease, we can give clinicians and patients more information. With that information, they can make more personalized decisions to improve their treatment and ideally, their lives.”

Read more about PanCuRx on OICR News.

January 25, 2019

Study reveals mechanism driving spread of advanced pancreatic cancer

Rob Denroche, bioinformatician and Project Leader of PanCuRx.

Large-scale pancreatic cancer study distinguishes primary from metastatic tumours, uncovering new genomic biomarkers that could help guide treatment selection

Over the next decade, pancreatic ductal adenocarcinoma (PDAC) – the most common type of pancreatic cancer – is projected to become the second leading cause of all cancer mortality. A better understanding of how PDAC changes when it metastasizes – or spreads from the pancreas to other organs – may help researchers find ways to treat the disease more effectively.

A study by OICR researchers and collaborators, published today in Cancer Cell, showed that the cells in advanced pancreatic tumours grow – or cycle – faster than those in early tumours, revealing one of the key reasons that the disease can advance so quickly.  OICR’s Pancreatic Cancer Translational Research Initiative, PanCuRx, investigated the whole genomes and transcriptomes of more than 300 PDAC tumours, contrasting cells from primary tumours and cells from metastatic tumours. This distinction may help clinicians advise patients about treatment, whether it be surgery, chemotherapy or radiation.

“Often, a patient’s primary pancreatic cancer recurs after surgery and chemotherapy, and there is limited knowledge of metastases to guide the next course of action. In less common ‘metachronous’ cases, treatment depends on whether the second tumour is new, or if it grew from remnants of a previous tumour,” says Dr. Ashton Connor, chief resident in the General Surgery training program at the University of Toronto and lead author of the study. “In this study, we explored differences between primary and metastatic tumours in the hopes of better understanding the mechanisms of cancer cell spread from the pancreas, and to ultimately inform their treatment.”

Over the last decade, PanCuRx has assembled the largest collection of genomic and transcriptomic data on primary and metastatic PDAC tumours. The initiative continues to collect samples through the COMPASS clinical trial today.

“There have been very few studies of advanced PDAC, so our rich dataset is very valuable to the future of pancreatic cancer research,” says Rob Denroche, bioinformatician, Project Leader of PanCuRx and co-author of the study. “Research groups from Germany, Brazil, Japan and across North America have been interested in the data that we’ve collected and we’re happy to enable their discoveries.”

PanCuRx collaborations span four continents, largely due to their enriched dataset on metastatic PDAC.

Through COMPASS, PanCuRx will continue to build on these findings and test if cell progression could be used to inform treatment selection in the clinic.

“This work is foundational to our understanding of advanced pancreatic cancer,” says Dr. Steven Gallinger, PanCuRx Director and Head of the Hepatobiliary/Pancreatic Surgical Oncology Program at UHN and Mount Sinai Hospital. “We look forward to building on this understanding to better inform treatment selection for those with this terrible disease.”

March 6, 2018

Canadian pancreatic cancer research team provides personalized medicine, new hope to patients

VANCOUVER – Canadian pancreatic cancer researchers are joining forces under a Terry Fox initiative bringing new hope for patients with this deadly disease.

“For many years it’s been hopeless from a patient perspective, and we are hoping to help shift this,” says Dr. Daniel Renouf (BC Cancer, University of British Columbia) who, along with Dr. David Schaeffer (UBC, Vancouver General Hospital), is leading a $5-million pan-Canadian, precision medicine initiative recently funded by the Terry Fox Research Institute.

A lack of early detection tests. Few known symptoms. Very limited treatment options. No known biomarkers that can be used to direct therapy.  These are among the clinical challenges team EPPIC, short for Enhanced Pancreatic Cancer Profiling for Individualized Care, is tackling over the next five years to improve personalized treatments for patients with pancreatic ductal adenocarcinoma (PDAC), a disease with just a nine per cent five-year survival rate.

Continue reading – Canadian pancreatic cancer research team provides personalized medicine, new hope to patients

January 30, 2018

Early results from COMPASS trial demonstrate benefits of using genomic sequencing to guide treatment for pancreatic cancer

Pancreatic Cancer and compass icon

Genomic profiling has allowed physicians to customize treatments for patients with many types of cancer, but bringing this technology to bear against advanced pancreatic cancer has proven to be extremely difficult. OICR’s pancreatic cancer Translational Research Initiative, called PanCuRx, has been conducting a first-of-its-kind clinical trial called COMPASS to evaluate the feasibility of using real time genomic sequencing in pancreatic cancer care. The research team recently reported early results from the trial, which show how they overcame the challenges of genomic profiling specific to pancreatic cancer and gained new insights about the disease.

PanCuRx is focused on improving treatment for pancreatic adenocarcinoma (PDAC), the most common form of pancreatic cancer and the fourth leading cause of cancer death in Canada. The group’s approach centres around understanding the genetics and biology of PDAC to inform the selection of therapies, as well as the development of new treatments.

Continue reading – Early results from COMPASS trial demonstrate benefits of using genomic sequencing to guide treatment for pancreatic cancer

September 29, 2017

OICR 2016/17 Annual Report

OICR Annual Report 2016/17

We are pleased to share the Ontario Institute for Cancer Research (OICR) Annual Report for 2016/17.

We are living in an era of unprecedented innovation in cancer research. Recent advances have helped us to better understand cancer and allowed for collaboration on a scale that was previously not possible. This work is happening now and it is happening right here in Ontario.

Continue reading – OICR 2016/17 Annual Report

May 25, 2017

OICR launches five all-star teams of Ontario scientists to tackle some of the deadliest forms of cancer

People from the press conference

Great strides have been made in cancer research, but much work remains to develop better treatments for the most lethal cancers and to advance new anti-cancer technologies. OICR is taking on a new approach, building on the success of the Institute’s first ten years and Ontario’s strength in particular cancer research areas. Reza Moridi, Ontario’s Minister of Research, Innovation and Science announced that the Institute is funding five collaborative, cross-disciplinary and inter-institutional Translational Research Initiatives (TRIs) with a total of $24 million over the next two years.

The TRIs will bring together some of the top cancer researchers in Ontario and be led by internationally renowned Ontario scientists. Each team will focus on a certain type of cancer or therapeutic technology. To maximize the positive impact of research on patients, the TRIs all incorporate clinical trials into their design. The TRIs, which were selected by an International Scientific Review Panel, are:

The funding will also support Early Prostate Cancer Developmental Projects led by Drs. Paul Boutros and George Rodriguez.

“In just over 10 years, the Ontario Institute for Cancer Research has become a global centre of excellence that is moving the province to the forefront of discovery and innovation in cancer research. It is home to outstanding Ontario scientists, who are working together to ease the burden of cancer in our province and around the world,” said Moridi.

“Collaboration and translational research are key to seeing that the innovative technologies being developed in Ontario reach the clinic and help patients,” said Mr. Peter Goodhand, President of OICR. “These TRIs represent a unique and significant opportunity to impact clinical cancer care in the province.”

Read the news release: OICR launches five large-scale Ontario research initiatives to combat some of the most deadly cancers

May 25, 2017

OICR launches five large-scale Ontario research initiatives to combat some of the most deadly cancers

Minister for Research, Innovation and Science

Toronto (May 25, 2017) – Reza Moridi, Ontario’s Minister of Research, Innovation and Science, today announced the Ontario Institute for Cancer Research is launching five unique, cross-disciplinary, multi-institutional Translational Research Initiatives (TRIs), each focused on a single type of or treatment approach to cancer. With $24 million in funding over two years, the TRIs will bring together world-leading scientists to tackle some of the most difficult to treat cancers and test innovative solutions to some of the most serious challenges in cancer today.

The TRIs build on Ontario’s proven strengths in areas such as stem cells, immuno-oncology, pediatric cancers, genomics, clinical trials and informatics. Working together, the province’s top scientists and clinicians will accelerate the development of much needed solutions for patients around the globe, with a focus on acute leukemia and brain, ovarian and pancreatic cancers. Each TRI includes clinical trials to maximize patient impact.

Continue reading – OICR launches five large-scale Ontario research initiatives to combat some of the most deadly cancers

February 10, 2017

OICR researchers to be part of Cancer Research UK’s Grand Challenge helping to answer cancer’s biggest questions

Technology and DNA

Toronto (February 10, 2017) – Ontario Institute for Cancer Research (OICR) researchers Drs. Lincoln Stein and Steven Gallinger have been announced as members of one of the first global research teams to be recipients of Cancer Research UK’s Grand Challenge.

The Grand Challenge aims to help overcome the biggest challenges facing cancer research in a global effort to beat cancer sooner.

Stein and Gallinger’s pioneering team will study samples from five continents to understand the DNA damage associated with different cancers, to understand what causes them and if they can be prevented. The project will be led by Professor Mike Stratton at the Wellcome Trust Sanger Institute, Cambridge, with collaborators from France, the U.S. and U.K.

Continue reading – OICR researchers to be part of Cancer Research UK’s Grand Challenge helping to answer cancer’s biggest questions

October 27, 2016

OICR’s Transformative Pathology Program contributes to recent PanCuRx findings

Ilinca Lungu, a Research Technician in OICR’s Transformative Pathology Program, talks about her group’s contributions to recent findings from the PanCuRx Translational Research Initiative.

Access to the Transformative Pathology Program’s resources and expertise is available to the research community through Diagnostic Development in OICR’s Collaborative Research Resources Directory. For more information about how you can access these services, visit oicr.on.ca/collaborative-research-resources.

October 21, 2016

OICR-led study finds four unique genomic signatures in pancreas cancer, uncovers potential of immunotherapies

The pancreas cancer puzzle

Pancreas cancer is one of the most aggressive and deadly forms of the disease. According to the Canadian Cancer Society, only 8 percent of pancreas cancer patients survive more than five years after diagnosis. OICR’s PanCuRx Translational Research Initiative has recently published the results of an international collaboration that increases understanding of this complex disease and how to treat it based on a patient’s unique profile.

Continue reading – OICR-led study finds four unique genomic signatures in pancreas cancer, uncovers potential of immunotherapies

October 12, 2016

New findings challenge current view of how pancreas cancer develops

Dr. Faiyaz Notta and Dr. Steven Gallinger

The findings provide important insights into how pancreas cancer develops and spreads and new strategies for better understanding one of the mostly deadly types of cancer.

Toronto (October 12, 2016) – Researchers in the multidisciplinary PanCuRx research initiative at the Ontario Institute for Cancer Research (OICR) and University Health Network’s Princess Margaret Cancer Centre, led by Dr. Faiyaz Notta and Dr. Steven Gallinger, today published new findings that challenge current beliefs about how and why pancreas cancer is so aggressive.

Continue reading – New findings challenge current view of how pancreas cancer develops

June 1, 2015

The Ontario Institute for Cancer Research invests $4.6 million to support pancreatic cancer research

TORONTO, ON (June 1, 2015) – Dr. Tom Hudson, President and Scientific Director of the Ontario Institute for Cancer Research (OICR) today announced OICR is investing $4.6 million over two years in PanCuRx, an initiative that seeks solutions to the high fatality rate of pancreatic cancer. The multidisciplinary program brings together researchers from the fields of genomics, pathology, cancer biology and informatics, as well as clinician scientists, who will collaboratively work to better understand pancreatic cancer on a molecular level and use this understanding to develop better, more personalized diagnostics and therapies for patients. The research will focus on pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer.

“There have been huge scientific advances over the past few decades on many types of cancer, but statistics on pancreatic cancer have remained largely unchanged,” said Dr. Tom Hudson, President and Scientific Director of OICR. “OICR is proud today to announce support for PanCuRx and help to improve these statistics and bring new solutions to patients.”

Initial funding for the initiative was provided last spring by Sylvia M. G. Soyka, director, and the Board of Trustees of the SMGS Family Foundation to the Canadian Friends of the Hebrew University (CFHU). The focus of this funding is to find and identify the molecular drivers behind metastatic pancreatic cancer. Researchers at the Institute for Medical Research Israel-Canada (IMRIC) at the Hebrew University of Jerusalem and Sheba Medical Center in Israel and at OICR in Toronto are currently working collaboratively to achieve this goal.

“This new funding will help tackle one of the least understood types of cancer. Ontario’s innovative and collaborative research community, together with our partners in Israel, are well suited for this challenge to discover new solutions and treatments that will benefit patients worldwide,” said Reza Moridi, Ontario Minister of Research and Innovation.

PanCuRx’s unique, collaborative design will allow teams of researchers to pursue research and clinical questions in parallel, with a tight link between clinical practice and lab research. The research will also be highly integrated with the Princess Margaret Cancer Centre’s translational PDAC program, ensuring that in addition to increasing understanding of the disease more generally, the research will directly inform the treatment strategy of patients who participate.

“The focus of PanCuRx is to ensure we bring the patients closer to the research and the research closer to the patients,” said Dr. Steven Gallinger, Surgical Oncologist and Head, Hepatobiliary/Pancreatic Surgical Oncology Program at University Health Network, Senior Investigator, Samuel Lunenfeld Research Institute of Mount Sinai Hospital and leader of the PanCuRx initiative. “By working together among disciplines and between the research and clinical components we feel much more can be accomplished and we have a real chance of making an impact on improving outcomes for PDAC patients.”

“I am alive today because of the groundbreaking treatment I received from Dr. Gallinger, Dr. Malcolm Moore and their team,” said Libby Znaimer, a prominent Canadian journalist and pancreatic cancer survivor. Znaimer received therapy targeted at the molecular level to the specific subtype of pancreatic cancer she was diagnosed with, an avenue of diagnosis and treatment that this new funding will further explore. “This summer I will celebrate seven years since diagnosis. We need more research to ensure that outcomes like mine become the norm, rather than a rare exception.”

Pancreatic ductal adenocarcinoma (PDAC) makes up approximately 85 per cent of pancreatic cancer cases. In 2014, an estimated 4,700 Canadians were diagnosed with PDAC and 4,400 died from the disease. It is the fourth leading cause of cancer death in Canada and the current five-year survival rate of 7.7 per cent is the lowest of all cancers. While the number of people dying from common cancers such as breast and colon cancer has dropped dramatically over the past 30 years, there have been only slight improvements for PDAC. It is estimated that PDAC will be the second leading cause of cancer death in North America within 10 years.