Study identifies two critical genes in pancreatic tumours

This new knowledge could lead to more personalized treatments for one of the deadliest forms of cancer.

In a study that has implications for understanding and treating pancreatic cancer, OICR-supported researchers have identified new genetic players critical for tumour growth in the pancreas.

Led by Dr. Daniel Schramek, a Senior Investigator at the Lunenfeld-Tanebaum Research Institute and Deputy Director of Discovery Research at Sinai Health, the researchers have identified two genes, USP15 and SCAF1, as tumour suppressors. People who have mutations in these genes are more likely to develop fast-growing tumours.

The team also found that mutations in USP15 and SCAF1 make tumours more susceptible to chemotherapy. This finding marks a significant step forward for a disease that has seen little progress in treatment options.

“While mutations in USP15 and SCAF1 make tumours more aggressive, they also sensitize tumours towards standard chemotherapy. And that means that you could stratify patients and they should have a better response to treatment,” said Schramek, who holds the Canada Research Chair in Functional Cancer Genomics and the inaugural Tony Pawson Chair in Cancer Research at Sinai Health.

The project was spearheaded by a former postdoctoral fellow, Dr. Sebastien Martinez, who is now a Senior Scientist at Centre de Recherche en Cancérologie de Lyon (CRCL) in France. The journal Nature Communications published the results.

Pancreatic cancer continues to have few treatment options with devastatingly low survival rates, under five years post diagnosis. According to one estimate, pancreatic cancer could be the second leading cause of cancer deaths in the United States by 2040.

Schramek’s team achieved their breakthrough by leveraging advances in genomic medicine, specifically tumour DNA sequencing, to identify mutations and genome editing technologies.

“Sequencing tumours allows you to find the genes that are affected and use that knowledge to develop treatments. But the problem is that every cancer has a plethora of mutations, and not all of them are disease-causing,” said Schramek, who is also an Associate Professor in the Department of Molecular Genetics at the University of Toronto.

Cancers often feature common mutated genes in many patients, along with hundreds of less frequent mutations that appear in a smaller subset. While mutations in USP15 and SCAF1 were found in fewer than five per cent of patients, their effect on cancer remained unclear.

Traditionally, tumour suppressor genes have been pinpointed by sequentially deleting genes in cancer cell lines and noting which deletions increase cell growth. However, these cell-based studies don’t replicate the tumour’s natural environment and interactions with the immune system, which are crucial for cancer progression. This likely explains why previous screens overlooked USP15 and SCAF1, according to Schramek.

A few years ago, Schramek’s team developed a genome editing approach enabling them to remove hundreds of genes simultaneously from individual cells in a single mouse. This method helps identify genes that, when absent, trigger cancer in the natural body environment.

Using this technology, the Schramek lab targeted 125 genes recurrently mutated in patient pancreatic tumors and pinpointed USP15 and SCAF1 as crucial tumor suppressors and potentially prognostic factors for chemotherapy response.

It just so happens that these genes are also absent in about 30 per cent of patients due to common genomic rearrangements in cancer, as Schramek has found.

This finding indicates that as many as a third of pancreatic patients who lack these genes might benefit from chemotherapy and have better outcomes.

“Historically, mutations in USP15 and SCAF1 would have been considered less important because they are not found in many patients,” Schramek said. “Our work shows that it is critical that we understand the functional consequences of these rare mutations as they can reveal new biology and therapeutic opportunities.”

This research was supported by funding from OICR, the Wallace McCain Centre for Pancreatic Cancer supported by the Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Canadian Cancer Society Research Institute, Pancreatic Cancer Canada and the Canadian Institute of Health.

This story was produced and originally published by Sinai Health and is available on the Sinai Health website. It is republished here with permission.

Ontario Institute for Cancer Research (OICR) applauds the Province’s renewed funding commitment to cancer research

OICR will continue to deliver innovative research and treatment solutions to help cancer patients live longer, healthier lives

The $144 million investment in the Ontario Institute for Cancer Research (OICR) announced today by the Government of Ontario will bring huge dividends for people affected by cancer and their families, now and into the future.

The funding — covering the next two years of OICR operations — was announced by Minister of Colleges and Universities, Jill Dunlop, as part of a large investment in Ontario’s research ecosystem.

“Ontario’s research institutes are making new discoveries and doing cutting-edge research that is significantly improving lives,” Minister Dunlop said in a news release. “This funding will help researchers continue to solve real-world problems, such as making clinical trials timelier and developing tools for earlier cancer diagnosis so Ontarians can live longer and healthier lives.”

OICR is the province’s cancer research institute. Since its inception in 2005, the Institute has helped make the province a global leader in cancer innovation, answering some of the biggest questions in cancer, and turning that knowledge into made-in-Ontario solutions.

Support from the Government of Ontario has allowed OICR to make groundbreaking discoveries that are changing the lives of people in Ontario and around the world. This continued provincial support will further drive OICR’s cutting-edge innovations, including blood tests that can find cancer earlier than a scan and treatments that harness our body’s own immune system to fight cancer.

“OICR’s continued commitment to research that meets the needs of patients gives me hope that people affected by cancer today, as well as future generations, will be able to live longer and live better,” says Terry Hawrysh, a blood cancer survivor and Chair of OICR’s Patient and Family Advisory Council.

OICR innovations are helping Ontarians live longer and healthier lives, while also making the province stronger. OICR, together with its strategic partner FACIT, continues to nurture local talent, turning Ontario-based discoveries into enterprises that attract significant investment and create high-value jobs in the province.

“The province’s support for OICR is an investment in the future of Ontarians and of people affected by cancer around the world,” says Dr. Laszlo Radvanyi, OICR President and Scientific Director. “We thank the Government of Ontario for their continued trust and vow to continue delivering solutions to improve the health of Ontarians and contribute to the province’s economic growth.”

Providence and Ontario Institute for Cancer Research (OICR) partnering to discover and develop mRNA therapeutics

Unique collaboration will combine OICR’s expertise in cancer genomics and translational drug discovery with Providence’s next generation of mRNA and LNP technology.

Calgary, Alberta and Toronto, Ontario, May 23, 2024 – Providence Therapeutic Holdings Inc. (“Providence”), a messenger RNA (mRNA) and lipid nanoparticle platform company engaged in the development of vaccines and therapeutics, and the Ontario Institute for Cancer Research (OICR), Ontario’s largest publicly funded cancer research institute delivering real-world solutions to people affected by cancer, today announced the signing of a collaboration agreement for mRNA drug discovery and development.

This is a unique collaboration that combines OICR’s expertise in cancer genomics and translational drug discovery with Providence’s next generation of mRNA and LNP technology to accelerate preclinical drug development and launch new clinical initiatives that answer key questions in clinical oncology.

“OICR and Providence share a common vision of advancing research in cancer prevention and treatment in Ontario, across Canada, and globally. We look forward to leveraging Providence’s next generation mRNA and LNP platform technology and drug development expertise alongside the experts at OICR to improve the lives of people battling cancer,” said Brad Sorenson, CEO and Founder of Providence Therapeutics.

“Partnering with an mRNA industry leader like Providence will help OICR harness our strengths in bioinformatics, genomics and immunology to generate new and exciting ways to prevent and treat cancer,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “I am especially excited for the impact this partnership will have for people affected by cancer as well as the potential economic value it can bring in helping drive Canada’s leadership in this rapidly growing field.”

OICR and Providence’s partnership will help advance modern drug development in Canada and create new clinical initiatives that will touch the lives of people across the country. As product development and manufacturing will be done domestically, Canadians will be first in line to participate in new clinical oncology programs and access new treatments.

All programs that emerge from this strategic partnership will result in guaranteed country-of-origin rights to Canada that will ensure Canadians will have affordable access to any medicines created.

About Providence Therapeutics

Providence Therapeutics has developed an mRNA medicines platform and has established itself as a competitive player within the mRNA scene for the last 10 years. Consisting of a clinically proven mRNA platform and a next-generation lipid-nanoparticle (LNP) platform, the company developed to enhance immune responses to cancers and infectious diseases. Along with this, Providence also has manufacturing and regulatory platforms that are capable of producing drugs for personalized vaccines up to pandemic scale amounts. Providence has a robust pipeline consisting of preclinical and clinical oncology, infectious diseases, and animal health programs. These programs have been developed internally and in collaboration with academic and industry partners that specialize in many different fields. For more information, please visit https://providencetherapeutics.com

About the Ontario Institute for Cancer Research

OICR is funded by the Government of Ontario. As the province’s cancer research institute, we take on the biggest challenges in cancer research and deliver real-world solutions to find cancer earlier and treat it more effectively. We are committed to helping people living with cancer, as well as future generations, live longer and healthier lives. For more information visit http://www.oicr.on.ca.

New “window-of-opportunity” clinical trials explore cutting-edge treatments for cancers of the liver, head and neck

Two new studies join the Ontario Institute for Cancer Research (OICR) portfolio of Window-of-Opportunity (WOO) Network clinical trials.

April 18, 2024, TORONTO – A new round of clinical trials supported by the Ontario Institute for Cancer Research (OICR) will harness a unique opportunity to test some of the newest treatment strategies for a range of different cancers.

OICR has announced two new clinical trials as part of its Window-of-Opportunity (WOO) Network, which brings together Ontario researchers, clinicians and patients to study the biology of newly diagnosed and recurrent tumours.

“‘Window-of-opportunity’ clinical trials take advantage of the two-to-eight-week period between the diagnosis of cancer and the surgery to remove the cancer, at a time when no treatment is happening,” says Surgical Oncologist, OICR Associate Scientist, and WOO Network Co-lead Dr. Angel Arnaout. “WOO Network trials capitalize on this window to study the biological effect of new cancer treatments without delaying or altering a patient’s primary treatment strategy.”

“Testing cancer therapies during this window of time allows us to understand and measure how they work against the tumour, and we’re very grateful to patients who participate in these studies and provide us this exceptional opportunity,” says WOO Network Co-lead Dr. Melanie Spears, who is also a Principal Research Scientist at OICR and Co-Director of the Institute’s Diagnostic Development program.

These latest WOO Network trials focus on liver cancer and head and neck cancers, and seek to understand how immunotherapies work alongside other innovative treatments to prepare a patient’s immune system to fight cancer. They will both also look for biological clues called ‘biomarkers’ that could indicate which patients would benefit most from different treatments.

Dr. Sara Kuruvilla and Dr. Anthony Nichols of the London Regional Cancer Program at London Health Sciences Centre (LHSC) and Lawson Health Research Institute will investigate the effectiveness of a novel immunotherapy drug combination before surgery to remove head and neck tumours, including monitoring how patients’ immune systems respond and if they experience fewer side effects from surgery. Findings are expected to provide preliminary evidence to support further evaluation of this approach in larger clinical trials.

“Recurrence is common after surgery for mouth and throat cancers, and surgical treatment can severely impact patients’ quality of life. We hope that receiving immunotherapy before surgery can improve a patient’s immune response, improve their outcomes and reduce the side effects they face.” – Dr. Sara Kuruvilla, Medical Oncologist at LHSC, Associate Scientist at Lawson, and Associate Professor of Oncology at Western University’s Schulich School of Medicine & Dentistry

Dr. Pablo Serrano and Dr. Brandon Meyers of Hamilton Health Sciences and McMaster University will study how a common immunotherapy (Durvalumab) impacts liver tumours after patients have stereotactic body radiation therapy (SBRT) but before they have surgery, with hopes that the combination strengthens patients’ immune systems to fight cancer.

“We aim to see if the combination of immunotherapy and radiation therapy can increase the number of immune cells that attack cancer, reduce the number of immune cells that allow cancer to grow, and potentially improve the prognosis of patients with liver cancer.” – Dr. Pablo Serrano, Scientist at Escarpment Cancer Research Institute (Hamilton Health Sciences and McMaster University) and Associate Professor of Surgery at McMaster University

These new clinical trials join OICR’s existing portfolio of WOO Network trials, which explore various therapeutic approaches and the impact they have on immune response in patients with a variety of cancers including lung, breast, pancreatic and bladder cancers.

OICR created the WOO Network in 2020 to help build Ontario’s capacity for state-of-the-art clinical trials by funding studies, mentoring new investigators and connecting scientists, clinicians, patient and industry partners.

“OICR’s WOO Network is a landmark program that leverages our capabilities in genomics and biomarker discovery to improve the drug development paradigm and better understand how new therapies work,” says OICR President and Scientific Director Dr. Laszlo Radvanyi. “In its third year of operation, the network is already yielding important insights about different types of cancers and the best ways to treat them. These newest trials will drive even more innovations to treat cancer more precisely and give patients the best chance at longer, healthier lives.”

“The Ontario government is proud to support new discoveries and innovations in cancer research by funding the work of OICR,” said Jill Dunlop, Minister of Colleges and Universities. “New clinical trials are key to testing therapies that have real-life impacts for patients in Ontario, ultimately helping them lead longer and healthier lives.”

About OICR
OICR is funded by the Government of Ontario. As the province’s cancer research institute, we take on the biggest challenges in cancer research and deliver real-world solutions to find cancer earlier and treat it more effectively. We are committed to helping people living with cancer, as well as future generations, live longer and healthier lives. For more information visit http://www.oicr.on.ca.

The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

Ontario cancer community comes together at OICR Translational Research Conference

Scientists, clinicians and patients shared their achievements and ideas for improving the lives of people affected by cancer.

For a moment, on stage in front of a crowd of accomplished cancer researchers from Ontario and beyond, Carla Bossart-Pletzer wondered if she belonged.

A designer and illustrator by trade, Bossart-Pletzer was serving as MC for OICR’s 2024 Translational Research Conference, a gathering of about 250 people from across OICR’s vast cancer research network.

“Then I remembered what my accomplishment is,” Bossart-Pletzer told the crowd. “My accomplishment is that I’m alive to be here – I’m surviving cancer.”

She said that her diagnosis of inflammatory triple negative breast cancer may have been a death sentence, if not for recent advances by cancer researchers.

“Thank you for what you’ve done and continue to do to give people like me a chance,” said Bossart-Pletzer, who has herself become a key contributor to cancer research as a member of OICR’s Patient and Family Advisory Council.

Bossart-Pletzer’s introduction set the tone the two-day conference – held March 26-27 in King City, Ont. – which showcased scientific innovations across many different disciplines, but was singularly focused on improving the lives of people affected by cancer.

The research presented at the conference took different approaches towards that goal. Some sessions covered new technologies for screening, diagnosing, monitoring and treating cancers, like liquid biopsy and novel targets for cancer drugs. Others focused on how to make research more accessible to diverse groups of people, and how to make sure promising research discoveries are implemented in the health system, where they can make a difference for patients.

The event was bookended by two impressive keynote speakers: Dr. George Kassiotis, a leading retroviral immunity researcher at The Francis Crick Institute, and Daphne Koller, CEO and founder of machine-learning driven drug discovery company insitro. And all conference sessions were co-facilitated by a person with lived experience of cancer, who helped to put the science into perspective.

The conference also put a spotlight on the next generation of scientists, including graduate students, postdoctoral fellows and early career researchers. Awards were handed out to the most exciting poster presentations by student researchers, including awards from the Ontario Rising Stars in Cancer Research Network and the new Acorn-2-Oak Commercialization Award from FACIT.

In his closing remarks, OICR President and Scientific Director Dr. Laszlo Radvanyi said the diversity of research presented at the conference is a testament to the infrastructure OICR has built. In addition to conducting and funding cutting-edge cancer research across the province, the Institute has helped make Ontario a global leader in genomics, liquid biopsy, genome informatics, artificial intelligence, radiopharmaceuticals, and other critical areas of cancer research.

“OICR is moving in the right direction. Let’s keep it up.”
Dr. Laszlo Radvanyi

PFAC Chair Terry Hawrysh applauded OICR’s emphasis on enabling early detection and intervention, while improving quality of life and reducing toxicities – outcomes he says matter to patients. He was also encouraged to see researchers focused on delivering these outcomes in an equitable and accessible manner.

“OICR is keyed in on the right things,” Hawrysh said. “I am walking away from this conference encouraged, with hope intact, and ready to roll up my sleeves and continue to work alongside you.”

FDA approves first cell therapy in landmark achievement for personalized medicine

OICR President and Scientific Director Dr. Laszlo Radvanyi reflects on the potential impact of a novel drug for metastatic melanoma, and his important role in the drug’s development.

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to a first-of-its-kind therapy that harnesses a patient’s own immune cells to fight skin cancer.

The drug, known as lifileucel (or Amtagvi^TM), is made by extracting cells called ‘tumour infiltrating lymphocytes’ (TIL) from a patient’s tumour sample and then using them to kill that same tumour.

The FDA approved lifileucel for patients with metastatic melanoma whose cancer could not be stopped by other treatments, making it the first TIL therapy approved for commercial use in North America. It also marks a significant achievement for Iovance Biotherapeutics, the U.S. biotech company behind it.

OICR President and Scientific Director Dr. Laszlo Radvanyi was Iovance’s founding Chief Scientific Officer (CSO) in 2014 and 2015 when it was initially established as Lion Biotechnologies. He and his team, together with then CEO Manish Singh, designed and built the company’s lab-office complex in Florida, recruited its initial scientists and lab technicians, and did the complex pre-clinical development work for Iovance’s first critical lifileucel trials in melanoma.

OICR News asked Radvanyi about the work that went into this groundbreaking therapy and what its FDA approval means for patients with melanoma and other cancers.

Why is this such an exciting development for patients with metastatic melanoma?

In this new era of personalized medicine, TIL therapy is about as personalized as it gets. It is made from a person’s own T cells, which are extracted, ‘expanded’ and infused back into the patient to kill the very tumour they came from.

The data from Iovance’s clinical trials has been tremendously exciting. Many people have had complete response after TIL therapy, meaning their cancer is completely gone. It is truly a life-saving therapy, and it will help make metastatic melanoma a survivable disease.

How significant is this achievement from a scientific perspective?

People have been trying to get a cell therapy to market for about 30 years, and they have generally been considered extremely difficult to commercialize. That’s because it’s a very difficult, involved process to manufacture cell therapies, and it can be time-consuming and costly.

When I helped launch Iovance as founding CSO, many people balked at the idea of advancing cell therapy and getting it approved by the FDA.

Well, we took up that challenge and did a huge amount of work to prove that it was safe and effective for patients and reduce the associated time and costs. My colleagues at Iovance and I showed that with hard work and creativity, we can do something no one thought could be achieved, and something that will make a major impact on the lives of people with cancer.

Does the approval of the first TIL therapy have implications beyond melanoma?

While this FDA approval is for metastatic melanoma, TIL therapy has the potential to be applied to all sorts of other tumour types. There are ongoing clinical trials for lung cancer, breast cancer, ovarian cancer and pancreatic cancer.

In my own lab at OICR, we are working to understand all the different antigens that trigger TILs to attack tumours. We’re exploring whether TILs recognize what are called ‘non-coding antigens’, which are considered great targets for cancer therapies. If so, that could open the potential for all sorts of other personalized TIL drugs.

What’s the status of TIL therapies in Canada?

While TIL therapies have not yet been approved for commercial use by Health Canada, I would love to see Canada approve this life-saving therapy as well as develop TIL manufacturing capacity in the future. Ironically, several Canadian scientists – including myself – were involved first-hand in establishing Iovance in 2014-2016 and laying the groundwork for the company’s success.

Canada also has many visionary leaders in the TIL field. This includes Dr. Pamela Ohashi and Dr. Marcus Butler at Princess Margaret Cancer Centre, who have been treating patients with TIL therapy as part of clinical trials. Dr. Simon Turcotte at the Centre Hospitalier de l’Université de Montréal has been active in establishing TIL manufacturing and clinical trials for melanoma and other cancers, while Drs. Brad Nelson and Robert Holt of BC Cancer have also been developing TIL therapy. Canadian biotech company Turnstone Biologics has also gotten into the TIL space through the acquisition of a California biotech, Myst Therapeutics, in 2021.

All this attests to our talent and capacity to be a significant player in the growing TIL therapy field in Canada. And there’s no reason why Canadians cannot use our own biomanufacturing expertise to advance and commercialize TIL therapies, like we did with an OICR-supported platform to manufacture CAR-T cell therapy in Canada through a consortium called BioCanRx.

As founding CSO of Iovance, I’m proud to have helped set things in motion for FDA approval, and proud of my colleagues there for realizing this landmark achievement. Now, as President and Scientific Director of OICR, I am excited to continue building capacity in Ontario and across Canada to develop novel therapies and get them patients who need them.

Do anxiety and depression affect our risk of cancer?

An international research project used Ontario Health Study data to investigate possible links between depression, anxiety and certain cancers.

Living with depression and anxiety has been thought to put people at a higher risk for certain cancers. New research from a large international study, which includes data from thousands of Ontario Health Study (OHS) participants, is showing otherwise.

In a recent paper published in the journal Cancer, the PSY-CA (PSYchosocial factors and CAncer incidence) project failed to demonstrate an association between depression and anxiety and breast, prostate, colorectal, and alcohol-related cancers, or cancers overall. However, it did find an association of depression and anxiety (both symptoms and diagnoses) with the incidence of lung cancer and smoking-related cancers. The paper noted that those associations were substantially reduced when adjusted for the presence of other known risk factors for lung cancers, such as smoking, alcohol use, and body mass index.

The PSY-CA Consortium is examining data from 18 study populations in the Netherlands, United Kingdom, Norway and Canada. Using information from cancer registries, this meta-analysis (a statistical analysis of multiple studies) looked at data collected from more than 300,000 adults to explore the relationship between specific psychosocial factors and a cancer diagnosis.

Dr. David Soave

Dr. David Soave of Wilfrid Laurier University led the OHS-related analysis for the PSY-CA project. He looked at data from 14,384 OHS participants. Other researchers looked at data from participants in two sister cohorts of the OHS, Atlantic PATH and CARTaGENE in Quebec.

He indicated the Ontario Health Study cohort of participants was well suited for the international project, as there was a substantial amount of information available on psychosocial factors that could be linked to known cancer diagnoses in the OHS study population.

OHS, which is hosted by OICR, is an ongoing research study involving more than 225,000 Ontario residents who are making their personal health information available to researchers.

The psychosocial factors explored in the study were:

Diagnosed depression
Diagnosed anxiety disorder and anxiety symptoms
Recent loss of a close family member or partner
Perceived low social support
Relationship status
General distress
Neuroticism

What should people take away from the study?

“Our results may be informative to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” said Soave.

He noted further research is still needed to understand how depression, anxiety, health behaviours and lung cancer are related.

***

This article was written by the Ontario Health Study and shared with permission. The original article is published at ontariohealthstudy.ca

National conference helps OICR PhD students shape their research and their futures

Several OICR-based PhD candidates were able to share their research at the 2023 Canadian Cancer Research Conference.

Surrounded by cancer patients, clinicians and hundreds of the brightest minds in Canadian cancer research, Rhea Ahluwalia felt a part of something bigger.

Ahluwalia was one of several OICR-based scientists and PhD students to travel to the 2023 Canadian Cancer Research Conference (CCRC) in Halifax. She says the people she met at the conference and the diversity of their perspectives helped her see beyond her own research “bubble.”

“I got to see the bigger picture, and how all of our work is like different cogs that keep the machine of cancer research moving forward to help patients,” says Ahluwalia, a University of Toronto PhD student based in Dr. Lincoln Stein’s lab at OICR. “It was really inspiring and made my work feel even more worthwhile.”

Ahluwalia shared her research, which involves using computational methods to understand the biology of neuroblastoma, as part of the CCRC poster sessions. She also gave a presentation during of one the conference’s sessions on paediatric cancers.

She says discussing her PhD project with colleagues across Canada was helpful to her current research as well as her future ambitions.

“I met and spoke with people from many different fields,” she says. “As a student, that helps me see what I could be looking at as a career in the future.”

CCRC is a biennial conference run by the Canadian Cancer Research Alliance. This year’s conference was held in-person for the first time since before the COVID-19 pandemic, and OICR was well represented. Dr. Trevor Pugh gave one of the opening plenary presentations, while OICR researchers spoke at various sessions throughout the three-day conference.

But the experience was especially invigorating for PhD researchers.

PhD student Farzan Taj – Ahluwalia’s colleague in Stein Lab – says the conference helped him refresh his knowledge on topics like artificial intelligence and learn about the latest innovations in precision oncology.

“The conference was a unique opportunity to interact with other researchers and have stimulating conversations about my work,” says Taj, whose conference poster was about using deep learning tools to predict how cancer cells will respond to treatments.

Stein Lab’s Xindi Zhang says she was inspired hearing from the many cancer patients and family members who attended the conference.

“They ignited my passion to deepen my understanding of cancer research, helped me realize the significance of my role as a research trainee, and motivated me to contribute more to advancing the field,” she says.

Zhang also received some valuable insights from colleagues that may help shape the future of her research project, in which she uses computational methods to classify the site and histology of tumours.

“I think it’s really important to connect with others who share your passion, gain diverse perspectives and contribute to the collective knowledge,” Zhang says.

Study shows that smoking ‘stops’ cancer-fighting proteins, causing cancer and making it harder to treat

In-depth analysis links harmful DNA mutations to tobacco smoking and other causes of cancer.

November 3, TORONTO — Scientists at the Ontario Institute for Cancer Research (OICR) have uncovered one way tobacco smoking causes cancer and makes it harder to treat by undermining the body’s anti-cancer safeguards.

Their new study, published today in Science Advances, links tobacco smoking to harmful changes in DNA called ‘stop-gain mutations’ that tell the body to stop making certain proteins before they are fully formed.

They found that these stop-gain mutations were especially prevalent in genes known as ‘tumour-suppressors’, which make proteins that would normally prevent abnormal cells from growing.

“Our study showed that smoking is associated with changes to DNA that disrupt the formation of tumour suppressors,” says Nina Adler, a University of Toronto PhD student who led the study during her postgraduate research in Dr. Jüri Reimand’s lab at OICR. “Without them, abnormal cells are allowed to keep growing unchecked by the cell’s defenses and cancer can develop more easily.”

Adler, Reimand and colleagues used powerful computational tools to analyze DNA from more than 12,000 tumour samples across 18 different types of cancer. Their analysis showed a strong link between stop-gain mutations in lung cancer and the telltale ‘footprint’ that smoking leaves in DNA.

The researchers then looked at whether how much someone smoked had an impact. Sure enough, their analysis showed that more smoking led to more of these harmful mutations, which can ultimately make cancer more complex and harder to treat.

“Tobacco does a lot of damage to our DNA, and that can have a major impact on the function of our cells,” says Reimand, an OICR Investigator and Associate Professor at the University of Toronto. “Our study highlights how tobacco smoking actually deactivates critical proteins, which are the building blocks of our cells, and the impact that can have on our long-term health.”

The study also identified other factors and processes responsible for creating large numbers of stop-gain mutations, which are also called ‘nonsense’ mutations. Some, like a group of enzymes called APOBEC that is strongly linked to stop-gain mutations in breast cancer and other cancer types, occur naturally in the body. Other factors like unhealthy diet and alcohol consumption are also likely to have similar damaging effects on DNA, but Reimand says more information is needed to fully understand how that works.

As for smoking, Adler says the findings from this study are an important piece of the puzzle behind a leading cause cancer in the world.

“Everyone knows that smoking can cause cancer, but being able to explain one of the ways this works at a molecular level is an important step in understanding how our lifestyle affects our risk of cancer,” Adler says.

OICR President Dr. Laszlo Radvanyi says these new insights should reinforce that tobacco smoking is one of the biggest threats to our health.

“This is further proof of the immense damage smoking has on our bodies, and further evidence that stopping smoking is always the right choice,” Radvanyi says.

OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit http://www.oicr.on.ca.

The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

First-ever national library of genomic data will help personalize cancer treatment in Canada and around the world

OICR will be playing a major role in the forthcoming Pan-Canadian Genome Library.

A groundbreaking initiative to unify genomic datasets from across Canada into a national library will drive innovations in personalized treatments for diseases like cancer, and OICR will be a major contributor.

The Canadian Institutes of Health Research (CIHR) announced $15 million in funding to create a Pan-Canadian Genome Library, a first-of-its kind resource for researchers, healthcare professionals and others looking to find and treat diseases more effectively.

The project will build on Canada’s global leadership in genomic research, which until now has been limited by the lack of a national approach to capture, store and access genomic data. This new library will provide a Canada-wide picture of diseases like cancer and the biology behind them, which will lead to new approaches to treating disease that are tailored to a person’s unique biology.

“Canada has several different projects and platforms that collect genomic information and patient data, but we do not have a consolidated infrastructure to connect all this information in an ethical and sustainable way,” says Dr. Mélanie Courtot, a Principal Investigator and Director of Genome Informatics at OICR. “By bringing these large datasets together, we can gain much more information about cancer and other diseases across the whole of the Canadian population.”

Courtot joins OICR’s Head of Adaptive Oncology Dr. Lincoln Stein and Associate Director of Adaptive Oncology Dr. Michelle Brazas in co-leading several key components of the library, including infrastructure, governance and outreach. The project will be led by Dr. Guillaume Bourque, Director of Bioinformatics at the McGill Genome Centre.

Courtot’s Genome Informatics team will leverage their expertise with other major databases like the International Cancer Genome Consortium (ICGC). This work will be supported by Overture, a data management software suite developed by OICR Genome Informatics that is driving genomic research in Canada and around the world.

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