Improving cancer detection with ultrasound and tiny droplets
With donors’ support, a team from Alberta is working to improve a cancer diagnostic tool using advanced ultrasound and nanotechnology.
Early cancer detection can lead to more successful treatment, yet currently available tests may not be sensitive enough to catch cancers early. One test known as a liquid biopsy involves detecting particles released by cancer cells, which can be used as biomarkers, in easily accessible bodily fluids like the blood. However, often not enough cancer particles are released for the cancer to be easily detected. Scientists are working on ways to increase the number of cancer particles released, which could allow easier detection of cancer through a liquid biopsy.
Dr Roger Zemp, a professor in the Department of Electrical and Computer Engineering at the University of Alberta, leads a team that studies and develops novel imaging techniques for various biomedical applications. The team first injected lab animals that had cancer with microscopic droplets that localized around the tumour. When they aimed powerful ultrasound beams at the droplets, the droplets burst and disrupted the tumour. This strategy successfully stimulated the release of more cancer particles into the blood, allowing for better detection of the tumour using a liquid biopsy approach.
“Detecting cancer biomarkers in blood tests is like finding a needle in haystack,” Dr Zemp explains. “Our approach stimulates the release of more biomarkers into the blood in a safe way. We add a lot more needles to the haystack.”
The cancer particles contained important genetic information about the tumour itself, including how aggressive the tumour would be. With further testing, this advanced technology could potentially lead to a new and improved diagnostic tool for cancer patients. This information could help doctors design a unique and effective treatment plan for people with cancer.
“We are excited about the potential of this new approach in helping diagnose cancer earlier and for helping doctors and patients make better informed decisions,” says Dr Zemp.
This research was published in January in the journal Cancer Research.
The writing of this summary was supported by a BioCanRx research communications internship.
Silence and resilience: Indigenous women’s cancer experiences
Understanding Indigenous women’s cancer experiences is an important step to improving their cancer care.
Full access to diagnostic and screening facilities, treatment and support systems are critical for the care of people who are affected by cancer. There are barriers that limit access to these resources among Indigenous communities, which could negatively impact their health. Indigenous women may additionally face gender inequality. Because Indigenous women’s individual experiences with cancer are not well documented, the challenges they face are not entirely addressed, nor have their strengths and resilience been described.
Dr Roanne Thomas, Canada Research Chair in Creative Practices and Well-Being based at the University of Ottawa, and her team learned about the cancer experiences of First Nations women who have survived cancer, along with their caregivers. To do this, they used interviews, story sharing activities and visual arts.
The silence around cancer is much more complex than previously thought. This research helps identify key areas that should be addressed in the development of more culturally appropriate cancer care in partnership with Indigenous people.
“This research simply would not have been possible without funding from the CCS,” says Dr Thomas. “Our team is particularly proud of our video which has been screened in communities several times in order to facilitate discussions about cancer experiences.”
This research was published in January in the journal Psycho-Oncology.
The writing of this summary was supported by a BioCanRx research communications internship.
A new way to classify ovarian cancers
With donors’ support, researchers are identifying genetic patterns in ovarian cancers that can lead to new treatment and diagnostic strategies.
Each person is unique because of their genetic blueprint (genome). Cancers also have unique genomes that distinguish them from one another. Cancers may differ from each other due to the mutational processes that change their DNA over time, which may make them more, or less, aggressive and resistant to treatment.
Comparing genomes across a group of cancers can reveal important information about how shared genetic patterns can distinguish different subtypes that may behave and respond to therapy in different ways.
At the BC Cancer agency in Vancouver, Dr David Huntsman, Dr Sohrab Shah and their teams studied the genomes of more than 130 ovarian cancers for this reason. They identified patterns of genetic mutations that reflected how well tumours can repair their DNA, which could help explain why some tumours come back after chemotherapy. Other tumours shared genetic patterns that reflected their propensity to evolve. Based on these findings, distinct subtypes of ovarian cancer can now be reclassified in a new way.
Researchers can now use these findings to improve diagnostic and treatment strategies for ovarian cancers, using more precise information. Further research is needed to complete our understanding of the cancer genome, and the team is eager to be a part of it.
This research was published in June in the journal Nature Genetics.
The writing of this story/article was supported by a BioCanRx research communications internship.
The tug of war between cancer and the immune system
Research by Dr Josie Ursini-Siegel and her team in Montreal reveals a new therapeutic strategy for breast cancer, thanks to donors' support.
The immune system is one of the body’s key defenses against cancer. Immune cells are equipped to survey the body to seek out and destroy cancer cells. Unfortunately, cancer cells are very smart and can learn to send out signals that allow them to escape from the immune system. While blocking these signals could help treat cancer, tumour cells often create many redundant back-up signals to ensure their survival.
Dr Josie Ursini-Siegel, a scientist at the Lady Davis Institute and an associate professor at McGill University in Montreal, discovered a core protein that is essential for breast cancer cells to suppress the immune system to allow them to grow. In a recent study, her team has now revealed even more about how this process works.
The protein, called ShcA, works in two ways in tandem. First, it sends immune-blocking signals to stop any immune attack on the breast tumour. Second, it makes the breast cancer cells less visible to the immune system, allowing the tumour to “hide” from its surveillance.
These findings unlocked a new target for breast cancer treatment. By blocking ShcA, the researchers could make breast tumours sensitive to cancer immunotherapies, which help the immune system mount an effective attack against the cancer. Further research will reveal whether blocking ShcA could be exploited as a novel treatment strategy for women with breast cancer.
“The continuing support of the Canadian Cancer Society has been instrumental to my team in allowing us to better understand the complexity underlying why some breast cancers develop resistance to immune attack,” Dr Urisini-Siegel says. “It further helped us to better identify groups of patients who are most likely to benefit from particular classes of immunotherapies.”
This research was published in March in the journal Nature Communications.
Searching for the next big treatment in sarcoma
Thanks to Canadian Cancer Society donors, Dr Torsten Nielsen is discovering new ways to treat a cancer most commonly seen in young people.
When cancer strikes young people in their prime, it can be particularly hard to deal with this diagnosis. Synovial sarcomas are aggressive cancers that arise most often in adolescents and young adults, in the soft tissues near the body’s joints. Recent research by Dr Torsten Nielsen and his team at the University of British Columbia has revealed a potential new therapeutic approach for these tumours that showed promise in the lab.
Despite traditional treatment with surgery, radiation and chemotherapy, synovial sarcomas still carry a high risk of spreading throughout the body. Only about half of the young people with this type of cancer will stay alive longer than 10 years, underlining the urgency of finding new ways to control or eliminate these tumours.
Toward this end, Dr Nielsen screened over 900 potential cancer drugs for their ability to stop synovial sarcoma cells in their tracks when grown in the lab. The most promising chemicals were a new histone deacetylase (HDAC) inhibitor similar to approved drugs, and proteasome inhibitors, drugs that have been used for over a decade to treat multiple myeloma.
Further study revealed that the HDAC inhibitor worked by counteracting the very molecular abnormality that drives synovial sarcoma. Combining it with a proteasome inhibitor made the treatment even more effective against synovial sarcoma cells in the lab than using either drug alone. In mice, the combination treatment successfully blocked tumour growth.
Dr Nielsen is particularly excited about this drug combination strategy because it could avoid a common pitfall that could stall turning this research into a new treatment – safety in patients. It turns out that similar drug combinations were recently shown to be safe in clinical trials in people with another type of cancer called myeloma.
“We’ve just written up a trial proposal and are busy trying to garner support from oncologists and drug companies as our next move,” Dr Nielsen explains. “We’re being helped by the Canadian Cancer Trials Group, which like my research lab, is being funded by donations to the Canadian Cancer Society.”
If shown to be successful in future clinical trials, this therapy could mark a significant step forward in improving treatment for synovial sarcoma.
This research was published in January in the journal PLOS ONE.
New designer viruses to fight aggressive brain cancer
With the support of CCS donors, Dr David Stojdl and his team are changing cancer treatment with cancer-fighting virus therapies.
Glioblastoma is the most common form of brain cancer in adults. It is very aggressive, growing and spreading quickly. Dr David Stojdl and his team at the Children's Hospital of Eastern Ontario Research Institute are designing viruses that trigger the body’s immune system to seek out and destroy glioblastoma.
They engineered a virus that uses the immune system to shrink aggressive brain tumours in mice. This exciting research is helping to design a new clinical trial. A worldwide patent on this new approach to brain cancer treatment has also been filed to accelerate the development of this therapy.
The cancer-killing virus technologies developed by Dr Stojdl’s team helped to form a Canadian company called Turnstone Biologics. Turnstone initially received a $11.3 million investment to support the development and commercialization of such designer viruses, and it has recently received an additional $41 million to help these treatments reach patients.
Dr Stojdl is the recipient of the Impact Grant of the Canadian Cancer Society and Brain Canada. You can find out more about his work at www.stojdllab.ca.
Keeping track of trends in cigarette contraband
With the support of Society donors, Dr Emmanuel Guindon has outlined trends in cigarette contraband in Canada.
Raising taxes on tobacco products like cigarettes reduces tobacco use and saves lives from cancer and other illnesses. But concerns have been raised that higher taxes also provide an incentive for manufacturers to sell and people to buy cigarettes illegally (known as contraband). In Canada this is an important problem. However, since it’s hard to measure participation in an illegal activity, estimates of how much cigarette contraband exists in Canada have been inconsistent and may be misleading due to the influence of tobacco manufacturers and organizations funded by them.
To address this gap, Dr Emmanuel Guindon at McMaster University, his team and colleagues at the University of Waterloo – Robin Burkhalter and Dr Stephen Brown – used data from different sources to study cigarette contraband in Canada over time. They focused especially on Ontario and Quebec, which have relatively higher contraband activity. Overall, they found a decreasing trend in cigarette contraband from 2007-2009, suggesting that anti-contraband government policies introduced around that time may have made an impact.
“The support from the Canadian Cancer Society allowed me to work with graduate students who were invaluable in our attempt to take a systematic and transparent approach, use different methods and multiple data sources to accurately describe trends in cigarette contraband in Canada,” Dr Guindon says. “Given the importance of price and tax in reducing tobacco use, I feel that our research will make it easier for us and others to track cigarette contraband in a timely manner.”
The full article describing this work was published online in September in the journal Tobacco Control.
Restoring the brakes on cancer
With the support of Society donors, Dr Michel Roberge is exploring new cancer treatments at the University of British Columbia.
Gene mutations can change the cell’s instructions on how to make important proteins. This can make cells produce shorter proteins that can’t do their normal job. If proteins that normally put the brakes on cell growth are disabled in this way, this can lead to cancer.
Since 1979, scientists have known that some antibiotics can fix the production of shortened proteins in the lab. However, the drug concentrations needed to accomplish this were too toxic for use in humans.
Decades later, Dr Michel Roberge and his team returned to re-examine this untapped resource to develop new cancer treatments. They discovered a new combination treatment that could restore full-length protein production in experimental model systems at much lower drug concentrations than an antibiotic alone.
If further testing is successful, this could lead to new treatments to restore the brakes on uncontrolled cancer growth. “We’re excited to explore this question further,” says Dr Roberge, “thanks to the continued support of Canadian Cancer Society donors.”
The full study can be found online, published in the journal Nucleic Acids Research.
Boosting survival in Li-Fraumeni syndrome
With support from the Society, Dr David Malkin at The Hospital for Sick Children is changing the outlook for people with a rare inherited cancer syndrome.
A rare genetic condition called Li-Fraumeni syndrome results from a mutation in a gene called TP53, a “gatekeeper” that controls how cells multiply and die. People with this inherited condition have a high risk of developing many types of cancers throughout the body, and these cancers often appear at a younger age than usual.
Dr David Malkin and his team previously developed a method of regularly screening people with Li-Fraumeni syndrome for early cancers using physical exams, imaging scans and blood tests. The approach is now referred to as the “Toronto Protocol”. The team has now shown that this screening method can detect cancers before patients have any symptoms, allowing for improved care. They also showed that Li-Fraumeni patients who participate in this surveillance protocol have dramatically higher 5-year survival rates compared to those who don’t.
These results will solidify the continued adoption of the Toronto Protocol at centres around the world. This study was published in August online in the journal Lancet Oncology.
Mapping cancers across Nova Scotia
Dr Louise Parker, the Canadian Cancer Society (Nova Scotia) endowed chair in population cancer research, works toward explaining Nova Scotians’ increased risk of bladder and kidney cancer.
For reasons that are still unclear, Nova Scotians have a higher risk for bladder and kidney cancers compared to other Canadians. Rates of these cancers are 25% higher than the national average or more.
To better understand what factors could be driving this problem, Dr Louise Parker and her team mapped out the distribution of bladder and kidney cancers across Nova Scotia. They found that the number of bladder and kidney cancer cases varied across different communities and identified high-risk areas. The increased risk for these cancers was largely stable over time, suggesting that Nova Scotians may be persistently exposed to unknown risk factors for bladder and kidney cancers.
This work will guide further research to help understand what factors underlie the increased cancer risk and how to plan public health initiatives to counteract this effect. The full text of this study is available online in the journal BMC Public Health.
ARCC conference explores sustainability of the cancer care system
Annual conference led by the Society-supported Canadian Centre for Applied Research in Cancer Control connects researchers across disciplines to improve cancer care.
On May 8 to 9, diverse stakeholders in applied cancer control research came together in Toronto for the 5th annual conference of the Canadian Centre for Applied Research in Cancer Control (ARCC).
ARCC is a pan-Canadian research centre designed to improve cancer control and cancer care spanning the spectrum of cancer prevention, screening, diagnosis, treatment, rehabilitation, survivorship and palliative care. ARCC provides interdisciplinary leadership focused primarily in the research areas of health economics, services, policy and ethics research, as well as education and knowledge translation. The Canadian Cancer Society is proud to provide core funding support to ARCC through our donors’ generous contributions, in order to expand research in these areas.
Since its launch in 2009, the ARCC network of researchers, healthcare professionals, policy-makers and trainees has grown to more than 800 members. Since 2012, ARCC has led annual conferences across Canada to connect researchers and healthcare decision-makers and share their collective knowledge.
The underlying theme of the 2016 ARCC conference was examining how to build a sustainable cancer care system, given that the number of new cases of cancer are expected to rise dramatically over the next 15 years. Presentations by Dr Michael Sherar (president and CEO of Cancer Care Ontario), Dr Jon Emery (professor at the University of Melbourne), Dr Doris Howell (senior scientist at the Princess Margaret Cancer Centre, University Health Network) and Dr Eshwar Kumar (co-CEO of the New Brunswick Cancer Network) focused on optimizing the use of human resources – like oncologists, family physicians, nurses, patients and caregivers – along the cancer care journey. This was complemented by sessions covering a variety of topics like the costs of cancer care and the importance of survivorship and follow-up care.
The conference, attended by over 170 participants, provided a welcoming atmosphere to connect across disciplines. A pre-conference “fireside chat” (complete with a virtual fireplace) gave attendees and esteemed panelists a chance to informally discuss how to effectively translate research evidence into action through the development and implementation of informed policies and programs. This was followed by a structured networking session reminiscent of speed dating, allowing each participant to connect with 12 others.
By connecting stakeholders in applied cancer control research across disciplines, this conference marked an important step towards creating innovative solutions to ensure that the cancer care system remains sustainable. We look forward to the next ARCC conference in 2017!
Reframing palliative care
Society-supported researcher Dr Camilla Zimmermann tackles how people with cancer perceive palliative care.
When people with cancer hear the term “palliative care”, many associate it with death and hopelessness. The resulting fear leads some patients to avoid or delay care that could significantly improve their quality of life.
Palliative care is designed to help people living with serious illnesses live better. It has been proven to improve quality life and is ideally offered to patients throughout the full course of their disease. Dr Camilla Zimmermann, a senior scientist at the Princess Margaret Cancer Centre and the head of the Division of Palliative Care at the University Health Network in Toronto, is trying to make early integration of palliative care the “new normal” for people with cancer.
Dr Zimmermann and her team interviewed advanced cancer patients who had been randomly assigned to receive palliative care early on in their disease in a clinic setting compared to those who received standard cancer care alone. Those who received early palliative care described deriving great benefit, but still felt the term itself carried a negative stigma.
This work highlighted the importance of educating the public, patients, families and healthcare providers about the benefits of early palliative care. “We need to rebrand or reframe palliative care to convey its importance for people living with cancer and their families throughout the cancer journey,” explains Dr Zimmermann. “By integrating palliative care earlier on in cancer treatment, we’ll be able to reduce suffering and improve overall quality of life in people living with this disease.”
This study was first published online in April in the journal CMAJ.
Dr John Dick honored with prestigious award
Dr John Dick, Society-funded researcher at the Princess Margaret Cancer Centre, was recently elected Fellow of the AACR Academy.
On April 5, the American Association for Cancer Research (AACR) Academy announced their election of 11 new fellows for 2016. Dr John Dick, a senior scientist at the Princess Margaret Cancer Centre, was nominated and elected as one of these fellows by his scientific peers for his outstanding achievements in cancer research.
This honor recognizes world-class researchers who have made significant contributions to innovation and progress in the fight against cancer. Research by Dr Dick and his team led to the discovery that acute myelogenous leukemia (AML) cells originate from cancer stem cells. This important finding helped explain how leukemia develops and could help guide the development of new therapies.
We are proud to have provided long-term support of Dr Dick’s research with more than $3 million over the past 22 years. Last year, he was awarded a Canadian Cancer Society Impact Grant of $1.25 million to continue his exciting work on understanding how AML starts and evolves.
The 2016 class of Fellows of the AACR Academy will be formally inducted at the annual AACR meeting later this month.
Studying cancer from the dark side
Alberta researchers are developing a new way to watch proteins in growing cancers, with Society support.
To understand how cancer works, researchers need tools to study it across a broad scale – from the big picture of how complex tumours grow within the body, down to fine-tuned knowledge of how different molecules interact. The ability to “light up” proteins with fluorescent tags has allowed researchers to study how proteins act in living cells and to non-invasively monitor how tumours grow in animals. The catch is that this technique only works for cancers found close enough to the skin’s surface that the fluorescence can be detected. What is missing is a way to study proteins in tumours growing deeper in the tissue.
With the support of an Innovation Grant from the Canadian Cancer Society, Dr Roger Zemp and his collaborator Dr Robert Campbell of the University of Alberta are developing a new technique called photoacoustic imaging to address this need. It uses new “dark” protein tags that don’t rely on fluorescence for detection. If successful, their new approach could give a detailed picture of how proteins talk to each other in tumours as they grow deep in animals’ tissues. Once further testing has been completed on promising candidate tags, this technique could help scientists study in detail how cancer starts and grows.
“Photoacoustic imaging is an exciting new technique that involves detecting ultrasound signals generated when laser pulses are applied to deep tissues,” says Dr Zemp. “With our new dark protein tags, we hope to use photoacoustic imaging to study the molecular basis of cancer in deep tumours. We hope that this will inform us on how cancers develop, how tumours respond to drugs, and how best to treat or even prevent cancer.”
This work was published in the journal Scientific Reports in March and can be accessed here.
Understanding drug resistance in prostate cancer
New insights from Society-funded Dr Artem Cherkasov and his team could help improve treatment for advanced prostate cancer.
Advanced prostate cancer is treated with specific hormone therapies. These drugs block a protein called the androgen receptor (AR) from interacting with pro-cancer hormones.
Even though new hormone therapies have been developed over the years, not every man with prostate cancer responds to them, and their cancer can unfortunately return. Understanding how resistance to hormone therapy develops could lead to new treatments to prolong prostate cancer survival.
Dr Artem Cherkasov, a researcher at the Vancouver Prostate Centre of the University of British Columbia, is working toward addressing this gap in knowledge. With the support of an Impact Grant from the Canadian Cancer Society, Dr Cherkasov and his collaborators have been studying how mutations in the AR gene can lead to drug resistance.
They recently discovered new AR mutations in DNA shed from prostate tumours into patients’ blood – an easily accessible bodily fluid for testing. The group then studied how different AR mutations lead to resistance to several hormone therapies used to treat prostate cancer.
All of the mutations studied allowed the cancer cells to escape the drugs’ effects. Some mutations even converted the drugs from AR blockers into AR activators. In contrast, they found that a new experimental drug could successfully block mutated AR, since the drug interacted with AR in a completely different way from current therapies.
Knowing how AR mutations lead to therapeutic resistance could help researchers and clinicians predict how men with prostate cancer will respond to existing hormone therapies, allowing them to provide personalized treatment recommendations. “These technologies bring us very close to fighting cancer in a real-time mode,” says Dr Cherkasov. This work could also help inform the design of new drugs to effectively treat this disease.
This important work was published in the journal Genome Biology in January and can be accessed here.
Why do treatments fail in recurrent childhood brain cancer?
Research by Society-funded Dr Michael Taylor at The Hospital for Sick Children could change how new treatments for medulloblastoma are tested.
Medulloblastoma is the most common form of brain cancer in children. If medulloblastomas recur despite standard treatment (surgery, radiation and chemotherapy), they are almost universally fatal. New treatments are clearly needed.
Personalized treatment, where the genetic abnormalities in an individual’s tumour are matched with an appropriate targeted therapy, may lead to improved outcomes with fewer side effects. However, targeted therapies have shown little promise in children with recurrent medulloblastoma. Research led by Dr Michael Taylor, a neurosurgeon and researcher at The Hospital for Sick Children, has now offered a simple explanation for why this has been such a challenge.
Dr Taylor and an international team compared medulloblastoma samples taken from children at diagnosis to those taken at recurrence. Children’s recurrent medulloblastomas had remarkably different genetics compared to their initial, pre-treatment tumours.
Clinical trials of new targeted medulloblastoma treatments have conventionally assumed that the targets in initial and recurrent tumours are similar. In these trials, children whose cancer has come back after standard treatment receive new therapies designed based on abnormalities in their diagnostic sample. By this time, however, the recurrent cancer may be driven by a new genetic profile.
This study highlights the need to rethink the design of clinical trials testing new drugs in medulloblastoma. The information it provides will help researchers and clinicians make a difference in the lives of children with brain cancer.
The full text of this study was published online in January in the prestigious journal Nature.
Remembering Dr Dan Dumont
We celebrate the memory of Society researcher Dr Dan Dumont (1960 – 2015).
We were saddened to receive news of the sudden death of Dr Dan Dumont, a researcher at the Sunnybrook Research Institute and professor at the University of Toronto, on December 17, 2015.
Dr Dumont led pioneering work in cell biology, studying endothelial cell growth and signaling, and its contribution to cancer. His scientific contributions, including the identification, cloning and mapping of the Tie2 gene (an endothelial cell tyrosine kinase receptor) have been recognized by several prestigious awards. Among these honors, Dr Dumont was awarded the Society’s William E. Rawls Prize in 2003 – an award given to a young investigator whose outstanding contributions have the potential for great impact on cancer control.
We have been fortunate to count Dr Dumont as a Society researcher. We are proud to have supported his research through Society grants from 2000 – 2005. We are also thankful for his service as a reviewer over many years, volunteering his time and expertise to help us select the best new research projects for funding across Canada.
Sharing his personal experience with lymphoma and colon cancer, he was an inspiring advocate for raising cancer awareness and the importance of funding cancer research. Dr Dumont will be remembered as a great scientist, collaborator, mentor and friend.
Redefining blood cell development
Research by Society-funded Dr John Dick’s team at the Princess Margaret Cancer Centre could provide clues to how blood cancers develop.
The blood is constantly renewing itself, generating new blood cells to replace old or damaged ones. Understanding how the body produces more than 10 different types of blood cells is key to understanding what goes wrong in blood cancers and other disorders.
The classic view is that blood stem cells produce a series of intermediate cells that gradually specialize in a stepwise process to serve different functions. Paradigm-shifting research by Dr John Dick and his team at the Princess Margaret Cancer Centre, however, has now redefined this process.
By developing new ways to study single stem cells, they showed that specialized blood cells develop much more rapidly from stem cells than previously thought. This new discovery could allow researchers to learn more about how different blood cancers develop, identifying new opportunities for personalized treatment.
The full text of this work, published online in the journal Science in November, is available here.
How do mutations affect gene activity patterns in cancer?
New computational tool developed by Society-funded Dr Sohrab Shah (shown here with student Jiarui Ding (left)) will help zero in on new targets for personalized cancer therapy.
Cancer develops as a result of a stepwise accumulation of gene mutations that allow cells to grow out of control. Advances in DNA sequencing technology have allowed researchers to detect all of the gene mutations in an individual tumour. However, to develop effective personalized treatments, they need to know which mutated cancer genes are the best to target.
To this end, researchers need to understand how each mutation affects cancer cells. However, they currently have few tools to do this. So far, computer models have focused mainly on the DNA sequence itself. Dr Sohrab Shah, a scientist at the BC Cancer Agency, believes that there is much more to the story and that researchers need to simultaneously analyze which genes are mutated and the functional consequences of these mutations.
With support from a Canadian Cancer Society Innovation Grant, Dr Shah and his team developed a new mathematical model and computational tool to analyze how gene mutations affected gene expression patterns in thousands of tumours from 12 different cancer types. They identified over 100 new suspected cancer genes and several mutations whose effects were similar across many cancer types. These findings will help prioritize the selection of genes for further study as new therapeutic targets to advance personalized medicine in cancer.
"Our new method helps to determine which mutations in cancer cells are altering biological activity,” says Dr Shah. “This work provides a path forward for integrated analysis of mutations and gene expression to further our understanding of biological processes gone awry in cancer and to improve the potential of identifying the most important mutations for personalized, targeted therapy."
The full text of this work, published online in the journal Nature Communications in October, is available here.
Accelerating the development of a new prostate cancer treatment
A new collaboration will advance a prostate cancer therapeutic developed by Society-funded Dr Robert Day toward the clinic.
The increasing burden of prostate cancer is a challenge that must be met with renewed efforts to prevent it, increase survival rates and improve the quality of life for men living with this disease. A new collaboration between the Institut de pharmacologie de Sherbrooke (IPS) and the Centre for Drug Research and Development (CDRD) is poised to make an impact by bringing a new prostate cancer treatment developed by Dr Robert Day closer to the clinic.
Prostate cancer is the third leading cause of death from cancer in men in Canada and is projected to be the most commonly diagnosed cancer by 2030. While hormone therapy is often effective in early stages, many prostate tumours develop resistance within a few years. Innovative, new treatments are therefore needed.
With the support of a Canadian Cancer Society Impact Grant, Dr Robert Day has been taking an outside-the-box approach to developing a new prostate cancer therapy. Dr Day, a researcher at the IPS at the Université de Sherbrooke, led pioneering work to establish the PACE4 enzyme as a promising therapeutic target in prostate cancer.
“Before our work began, the idea of targeting PACE4 to treat cancer was not well understood, nor was it on anyone’s radar. Since then, our work has provided the proof-of-concept that inhibition of PACE4 blocks cancer growth through a fundamentally new approach,” Dr Day explains.
Dr Day and his team designed and developed an inhibitor of PACE4 that was both potent and stable when injected into mice. In mice with growing prostate tumours, the PACE4 inhibitor shrunk the tumour size by 60% in under 3 weeks, compared to controls.
The collaboration with the CDRD, Canada’s national drug development and commercialization centre, will advance the clinical testing and commercialization of this new candidate therapeutic. The first step is to develop a formulation of the PACE4 inhibitor that is stable in the human body and can be administered in a more convenient pill form. Additional studies will establish its safety and side effect profile.
“We’re very excited to see this new treatment approach taking steps toward the clinic,” says Dr Day, “If successful, this collaboration could be a great example of how results from the lab can translate effectively to improved patient care.”
Connecting with the cancer research community at the CCRC
Researchers from across Canada and beyond connected at the 2015 Canadian Cancer Research Conference in Montreal.
The 2015 Canadian Cancer Research Conference (CCRC)
was held November 8th to 10th in Montreal. This conference, which occurs every 2 years, brings together the Canadian cancer research community spanning the entire research spectrum, from cancer prevention to end-of-life care and from basic discovery research through translation to clinical practice and policy.
The Canadian Cancer Society was a major supporter of the conference and many Society-funded researchers contributed to the high caliber scientific program. Attendees learned about recent advances in areas as varied as immunotherapy, cancer prevention and global cancer control, and personalized medicine, among others. Many Society staff from across the country attended the conference and acted as ambassadors to share information about our mission, research programs at the Canadian Cancer Society Research Institute (CCSRI) and our publications at an information booth located in the poster exhibition hall.
CCSRI also played a key role in satellite meetings and workshops designed to complement and build on the CCRC experience. CCSRI partnered with the Canadian Institutes of Health Research’s Institute of Cancer Research (CIHR-ICR) to host a satellite meeting for new faculty and senior postdoctoral fellows to provide strategic education and mentoring opportunities for the next generation of great cancer researchers. Following the conference, the Society’s Prevention Network
also held a full-day workshop entitled “Cancer Prevention: Science and Society” to define strategic prevention priorities and explore opportunities for interdisciplinary collaboration from research, policy and program perspectives.
We look forward to the next CCRC in 2017!
Studying leukemia from different angles
Society-funded researcher Dr Guy Sauvageau studied 2 important forms of acute myelogenous leukemia (AML) in Montreal.
Acute myelogenous leukemia (AML) can be found in several forms with different molecular features and patient outcomes. Learning more about the molecular characteristics of AML can improve diagnosis, prognosis and therapy for this blood cancer. Dr Guy Sauvageau, director of the Molecular Genetics of Stem Cells research unit and a principle investigator at the Institute for Research in Immunology and Cancer (IRIC), led a study of 2 forms of AML characterized by abnormalities in the MLL gene that often have poor outcomes.
By sequencing DNA from AML cells and measuring gene activity, the researchers – for the first time – identified a pattern of gene activity shared by these 2 AML subsets. They also tested how the cells responded to multiple anticancer drugs and found a subset of AMLs whose mutations made it particularly susceptible to certain combination treatments. The wealth of information gathered about gene activity in AML should improve how it is diagnosed and how treatments can be tailored to improve survival.
The full text of this work, published online in August in the journal Nature Genetics, is available here
Modelling drug responses of human lung cancers in mice
Society-funded researcher Dr Ming-Sound Tsao (shown here with co-authors Erin Stewart (left) and Dr Frances Shepherd (right)) uses mice to realistically model human lung cancers and their response to drugs at the Princess Margaret Cancer Centre.
The growth of many non–small cell lung cancers (NSCLCs) can be driven by a mutated version of EGFR, a protein that signals cells to multiply. Several available drugs targeting EGFR are used to treat lung cancer, including afatinib (Giotrif), erlotinib (Tarceva) and gefitinib (Iressa). While many individuals initially respond to these drugs, almost all of them eventually develop resistance and their disease progresses.
To test new lung cancer treatments and identify biomarkers to predict who is most likely to respond to them, researchers need experimental models that realistically mimic human lung cancer so they can study it in the lab. One type of model relies on implanting fresh tissue from human lung tumours into mice. These are called patient-derived xenografts, meaning a graft (or implant) of tissue from a different species (human into mouse). While these models can be difficult to develop, they offer great opportunities for researchers to study the biology, response to therapy and mechanisms of drug resistance in human lung cancer.
Supported by the Society, Dr Ming-Sound Tsao, a Senior Scientist at the Princess Margaret Cancer Centre in Toronto, is studying how the molecular features of early stage NSCLCs can be exploited to improve treatment and survival. Dr Tsao and his team successfully generated mouse xenograft models from 6 different tumours from people with NSCLC that had EGFR mutations. The mouse models accurately mimicked the appearance and molecular features of each person’s original tumour. They also had variable responses to drugs blocking EGFR that closely mirrored how the corresponding tumour behaved in the human body. In one case, where the person’s lung tumour was resistant to therapy, the researchers were able to identify molecular features that made the lung cancer dramatically susceptible to an alternative therapeutic approach in the mouse.
These mouse models can be used not only to understand what makes each person’s lung cancer grow, but also to identify new opportunities for targeted, more personalized treatment. “Mouse models derived from patient tumours may speed up the development of new cancer drugs and improve patient selection for emerging molecularly targeted treatments,” comments Dr Tsao.
This research was supported by 3 grants from CCSRI to Dr Tsao, including the Rachelle Archambault Innovation Grant.
The full text of this work, published online in June in the Journal of Clinical Oncology, is available here
Current Oncology calls for papers on health economics in cancer
Submit papers on Canadian cancer costing research for a special issue of Current Oncology by September 30, 2015.
The journal Current Oncology will be publishing a special supplemental issue on "Original Canadian cancer costing research". This supplement will be co-edited by Dr Nicole Mittmann (Cancer Care Ontario, Toronto, Ontario) and Dr Claire de Oliveira (Centre for Addiction and Mental Health, Toronto, Ontario).
Current Oncology is a peer-reviewed journal that focuses on Canadian oncology practice and studies of international significance. Researchers are encouraged to submit appropriate manuscripts by September 30, 2015.
The full details and submission instructions can be found here
A new ultrasensitive blood test for cancer biomarkers
Innovative method to detect cancer mutations developed by Society-funded researcher Dr Shana Kelley at the University of Toronto.
New methods to recognize molecules in the blood that reliably detect cancers and track how they respond to treatment could change the way cancers are diagnosed and managed. Tumours can shed molecules into the bloodstream that carry information about mutations found in the cancer cells, which researchers are studying for their potential as cancer biomarkers. These approaches have advantages over traditional biopsies that can be invasive to patients and challenging for some cancers that are not readily accessible in the body.
Dr Shana Kelley and her group developed a new, extremely sensitive test that uses sensors on a chip to detect cancer mutations in blood samples. They used their new chip to detect key cancer-driving gene mutations in blood samples from people with lung or skin cancers. While the underlying technology is complex, the non-invasive test was simple to perform, fast (as short as 5 minutes) and could be automated to keep costs low. They are developing this technology to be used in the clinic as an alternative to tissue biopsies to detect cancer, monitor how each patient responds to therapy and tailor treatment decisions.
“Our chip-based approach to detecting cell-free nucleic acids provides a straightforward and sensitive way to look for tumour-related sequences using non-invasive sampling,” says Dr Kelley, “and we are excited about its application to the further development of liquid biopsy-based patient monitoring.”
The full text of this significant research, published online in June in the journal Nature Chemistry, is available here
Society-funded cancer researchers appointed to Order of Canada
Drs Janet Rossant, Mary Gospodarowicz, James Rutka and Martin Yaffe received prestigious national honours on Canada Day
On July 1, 2015, Drs Janet Rossant, Mary Gospodarowicz, James Rutka and Martin Yaffe were among 100 individuals appointed to the Order of Canada, one of the highest civilian honours in the country. The Order recognizes 3 tiers of recipients – Companions, Officers and Members – for outstanding achievement, dedication to the community and service to the nation.
Dr Rossant, Chief of Research Emeritus at The Hospital for Sick Children (SickKids) and Professor at the University of Toronto, was appointed Companion of the Order of Canada (the highest tier) for her outstanding contributions to developmental and stem cell biology and her national and international scientific leadership.
Dr Gospodarowicz, Medical Director at the Princess Margaret Cancer Centre and Professor at the University of Toronto and Dr Rutka, Neurosurgeon and Senior Scientist at SickKids and Professor at the University of Toronto were appointed Officers of the Order of Canada. Dr Gospodarowicz was recognized for her contributions to improving cancer radiotherapy and her leadership in advancing cancer care worldwide.
Dr Rutka was honored for his role in advancing the treatment of brain cancer in children and his international leadership in neurosurgery.
Dr Martin Yaffe, Senior Scientist at the Sunnybrook Research Institute and Professor at the University of Toronto, was appointed Member of the Order of Canada for his scientific breakthroughs in breast cancer screening and his commitment to improving women’s health.
All 4 recipients have been supported by Society funding and we have been fortunate to have partnered with them. We congratulate all recipients on their great achievements!
Understanding molecular variation within each prostate tumour
Dr Robert Bristow at the Princess Margaret Cancer Centre breaks ground on understanding molecular differences between distinct regions in prostate tumours.
Not all prostate cancers behave the same, even when the tumours have similar clinical features. One possible explanation for this tumour-to-tumour variability is that each tumour contains a unique molecular makeup. Dr Robert Bristow – recipient of a Canadian Cancer Society Research Scientist Award – and a team from the Canadian Prostate Cancer Genome Network studied DNA from prostate tumours from several men, examining multiple distinct regions to create “portraits” for each sample. They found many differences in the genetic abnormalities present in each region of each single tumour. They also discovered a new role for the MYCL1 gene in prostate cancer. “The ability to understand the unique genetics of each tumour within a man’s prostate gland means that we can now understand the big picture of the cancer,” comments Dr Bristow. This may provide important information for tailoring treatment to each individual as personalized medicine.
The full text of this important research, published in the journal Nature Genetics, is available here: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3315.html
Examining the link between breast stem cells, aging and cancer
Society-funded research by Dr Rama Khokha at the Princess Margaret Cancer Centre used a mouse model to study how stem cells impact aging breast tissue.
Given that age is the primary risk factor for breast cancer in women, it is important to understand what occurs during aging that contributes to cancer development. It has been suggested that stem cells ultimately lose their capacity to regenerate tissue with age, resulting in the degeneration of aging tissue. Dr Rama Khokha and her group made an important link between stem cells, aging and breast cancer. Published in the journal Nature Cell Biology, Dr Hartland Jackson from the Khokha lab discovered a set of genes that increase the number of stem cells in the mammary (breast) tissue of old mice, preserving the tissue's health. Contrary to the current belief that more stem cells increase cancer risk, the extended breast tissue lifespan in this study was not associated with an increase in breast cancer induced by a chemical. "Understanding how stem cells maintain our tissues is important for the prevention of all diseases associated with aging, including cancer," says Dr Khokha. These findings suggest an opportunity to harness a biological process to curtail aging and benefit stem cell therapy for tissue regeneration, without altering cancer susceptibility.
This study was supported through the former Canadian Breast Cancer Research Alliance.
The full text of this important research, published in the journal Nature Cell Biology, is available here: http://www.nature.com/ncb/journal/v17/n3/full/ncb3118.html
Hookah use among youth in Canada is increasing in popularity
Society-funded research by Dr Steve Manske at the Propel Centre for Population Health Impact found that hookah use among high school students is a growing concern.
Cigarette smoking is decreasing in North America, but there is an increased consumption of alternate tobacco products. One alternative, shisha tobacco, is conventionally smoked through a water pipe, also known as a hookah. A hookah is a traditional Middle Eastern pipe, but is becoming more prevalent among youth and young adults across the world. Studying data from the national 2012-2013 Youth Smoking Survey, Dr Steve Manske and his group at the Propel Centre for Population Health Impact described the prevalence of use and perceptions of the safety of hookah smoking among Canadian grade 9-12 students. They found that about one in twenty students reported currently using hookah, and that use has increased since 2010. They also discovered that among hookah users, flavored tobacco was a popular choice. Equally concerning was that over a third of students believed that hookah smoking was less harmful than cigarettes, and those with that opinion had a much greater likelihood of using a hookah. These findings highlight the need for better surveillance of hookah use, in addition to traditional cigarettes, and can be used to inform policy on tobacco control.
The full text of this important research, published in the journal Cancer Causes and Control, is available here
Dr Janet Rossant receives latest Canada Gairdner Award
SickKids Chief of Research Dr Janet Rossant named the recipient of 2015 Canada Gairdner Wightman Award.
The Canadian Cancer Society is thrilled to congratulate Dr Janet Rossant on receiving the 2015 Canada Gairdner Wightman Award. Dr Rossant, Chief of Research and Senior Scientist at The Hospital for Sick Children and Professor at the University of Toronto, is being recognized for her outstanding scientific contributions to developmental biology and stem cell research, and her national leadership in advancing research programs aimed at improving children’s health. This award is given to a Canadian scientist who has demonstrated outstanding leadership in medicine and medical science. Dr Rossant is an internationally recognized scientist who has made significant contributions to the understanding of stem cells, paving the way for novel therapies against several diseases, including cancer. She has also held many vital leadership roles in the scientific community, including President of the International Society for Stem Cell Research, Deputy Scientific Director of the Canadian Stem Cell Network, and Director of the Ontario Institute for Regenerative Medicine. The Society has been proud to support Dr Rossant’s research and fortunate to benefit from her years of service on grant review panels.
Research suggests a new treatment option for prostate cancer
Society-funded research by Dr Robert Day at Université de Sherbrooke has identified PACE4 as a therapeutic target for prostate cancer.
One of the first Impact grants ever awarded is paying dividends. While blocking the male hormone, androgen, is effective in the early stages of prostate cancer, it eventually fails after 2-3 years. With an Impact grant, Dr Robert Day and his team at Université de Sherbrooke are developing a new therapeutic approach from a completely separate angle, by targeting the growth of cancer cells through the enzyme PACE4. In the journal Oncotarget, they provided the first proof of concept that blocking PACE4 stops prostate cancer progression in mice. This significant finding could lead to a new therapeutic strategy for prostate cancer.
The full text of this important research, published in the journal Oncotarget, is available here: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2918&path%5B%5D=6327
Risk assessment for hereditary stomach cancer
Society-funded research by Dr David Huntsman at BC Cancer Agency has generated reliable estimates for stomach cancer risk in CDH1 mutation carriers.
A rare but aggressive form of stomach cancer is often difficult to detect early enough to provide effective therapy. While it is known to be hereditary, accurate risk assessments for individuals with particular gene mutations are lacking. Dr David Huntsman’s group sought to help people who carry a particular gene mutation understand what their individual risks are of developing hereditary stomach cancer. By analyzing the genetics of nearly 4,000 individuals from 75 families who have a history of this cancer, they determined that men and women who carry mutations in the CDH1 gene have a 70% and 56% chance of developing stomach cancer, respectively. They also identified a number of other genetic mutations that may increase one’s risk, but more work needs to be done to calculate the risk they pose. These findings will have immediate influence on clinical care – when to start screening, how often to be screened and whether to undergo preventive surgery.
The full text of this important research, published in the journal JAMA Oncology, is available here: http://oncology.jamanetwork.com/article.aspx?articleid=2108851
Recent publications by NCIC Clinical Trials Group
Read about high-impact findings from the Society-funded clinical trials network
NCIC CTG publication looks at bone density effects of a drug that reduces breast cancer risk
A new paper by the Society-funded NCIC Clinical Trials Group may help women who are at risk of developing breast cancer make more informed decisions about preventive measures. Exemestane, an aromatase inhibitor, was the subject of a significant finding by NCIC CTG earlier this decade. The drug was found to reduce the risk of breast cancer by 65% in women at increased risk of developing the disease.
This remarkable discovery was followed by an investigation for side effects, which found that postmenopausal women on exemestane may experience poorer bone density compared to those who were not. The findings, published in Lancet Oncology, recommended that women at risk of developing breast cancer and with a low bone mineral density score be prescribed aromatase inhibitors in conjunction with bisphosphonates to preserve their bone health.
The Lancet Oncology, Volume 15, Issue 4, Pages 474–482, April 2014
NCIC CTG phase 3 trial suggests new targeted treatment options for soft tissue sarcoma
A multi-centre trial across 10 countries has tested the ability of a drug regimen to improve survival in a form of advanced cancer. In this trial, patients with advanced, inoperable or metastatic high-grade soft tissue sarcoma were randomized to receive either doxorubicin alone, or doxorubicin combined with ifosfamide. While there was no significant difference between groups for overall survival, the group taking both drugs experienced a longer period without cancer progression (and with improved control of tumours). However, the combined drug regimen also led to more toxic effects among patients. These findings, published in Lancet Oncology, could lead to more individualized treatments for patients with this cancer, so they and their clinicians can weigh priorities in choosing treatments, considering a patient’s tolerance for side effects and the benefits associated with controlling existing tumours.
The Lancet Oncology, Volume 15, Issue 4, Pages 415–423, April 2014
Last modified on: December 15, 2017