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Pancreatic cancer rising ...
Sep 5, 2019 -
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Research Grants Awarded

Project #1:

Funded by: Craig’s Cause Pancreatic Cancer Society Research Grant

Project Title: "Duodenopancreatectomy versus Best Supportive Care for Pancreatic Adenocarcinoma."

Researcher: Dr. Michele Molinari, Associate Professor, Department of Surgery and Community Health, Dalhousie University

Project Cost: $40,200.00

Update: Many surgeons and physicians have been considering that the Whipple procedure is only a palliative therapy. In their opinion, the results are not good enough to suggest that the Whipple procedure should be offered to patients. Although they realize that without undergoing surgery, the mean survival is only 6 months, these doctors say that most of the patients with pancreatic cancer are quite advanced in their age and therefore they should not be operated on.

No previous research has focused attention to the patients' perspective. As physicians, we recommend some treatments because they are the only available potential way to cure. Despite the fact that the Whipple fails for the majority of our patients, we are able to cure a few of them. Is that sufficient to support surgery for everyone? We don't know.

My interest is to find out. The Probability-Trade-Off (PTO) interview will provide us with an understanding as to what patients with pancreatic cancer, would decide if fully informed about their condition and the options available to them.

PTO is a formal, structured interview that makes patients go through a clinical situation. After being fully informed about the nature of the disease, the probabilities of success and failure, the patients are asked to choose between two or more treatments. Then, the probabilities of success and failures are changed in a progressive way so that one treatment becomes more appealing over the others. The difference between the starting probability and the probability when the patient changes her/his mind is called Minimal Probability Trade Off that the individual is willing to accept to undergo a therapy that is more invasive but that can potentially provide a better long term outcome.

This research technique is quite new and has not been used before for pancreatic cancer.

Outcome: Currently in progress.


Project #2

Funded by: Cancer Research Training Program (CRTP) Award, Partnership between Beatrice Hunter Cancer Research Institute and Craig’s Cause Pancreatic Cancer Society

Project Title: "Treatment Provided to NS patients, is it Optimal?" / "CRTP General Public Summary"

Researcher: Dr. Scott Hurton

Budget: $36,000.00 (0ver 2 years)

Update: Dr. Scott Hurton was awarded the "The Colleen Elliott Award." Established in 2011, the Colleen Elliott Award was created to honour excellence in cancer research training and is awarded to a research trainee who demonstrates the greatest promise and potential for excellence in cancer research.

Pancreatic cancer PC is a deadly malignancy, and although difficult to detect in early stages and treat, it can sometimes be cured through surgical resection. The pancreas lies behind the stomach, and is close to the liver, duodenum, and bile duct. It produces and releases hormones such as insulin into the bloodstream and digestive enzymes into the small bowel.

Research has shown that some patients are not referred for surgery or chemotherapy, even though there is an increase in survival. It is unknown how many PC patients in Canada receive the most current treatment through their illness, and we are concerned that patients with PC do not receive the highest quality of care in Nova Scotia.

We will study a group of patients who developed PC in Nova Scotia over the past ten years, and this information will be used to examine the treatment of these patients. We will examine the quality of care we provide to them, by looking at the treatments they receive and see how many patients are receiving treatment according to the most recent evidence. This will ensure that we are using the most up to date evidence on treatment after surgery for PC. We plan to take this one step further and examine some of the reasons why patients do not receive the recommended treatment. This will allow us to change the way we manage these patients, and potentially improve their quality of life during their treatment.

The information from this study will lead to future research that will further examine the healthcare resources used by PC patients. This may allow us to use these resources for PC patients to improve their quality of life and potentially prolong their survival.

Project #3

Funded by: Cancer Research Training Program (CRTP) Award, Partnership between Beatrice Hunter Cancer Research Institute, and Craig’s Cause Pancreatic Cancer Society

Project Title: "The Role of P11 Protein in Pancreatic Cancer" / "CRTP General Public Summary"

Researcher: Moamen Bydoun (Supervisor, Dr. David Waisman, Department of Biochemistry and Molecular Biology, Canada Research Chair in Cancer Research) CLICK HERE FOR CV

Budget: $36,000.00 (Over 2 years)

Update: Moamen Bydoun won best platform presentation at the Beatrice Hunter Cancer Research Institute's bi-annual Cancer Research Conference held this past November. His talk titled The Plasminogen Receptor P11 Contributes to KRASG12Ddriven Invasiveness of Pancreatic Cancer Cells and is Upregulated in Human Pancreatic Tumors was one of six presentations selected to presented orally at the conference.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in North America. Less than 5% of patients survive more than five years after being diagnosed. The lethal nature of this cancer is mostly attributed to its ability to invade and occupy other vital organs of the body such as the liver, spleen, lungs and brain in a process called “metastasis”. Once metastasis is established, pancreatic cancer renders extremely difficult to treat with current therapies. More studies are then required to further understand the underlying biology of metastasis in pancreatic cancer in the hopes of developing new drugs targeting this process.

In our laboratory, we have established that a surface protein called p11 is an essential element in allowing cancer cells to become invasive, leave primary cancer sites, and reach the bloodstream eventually leading to metastasis. Depleting cancer cells from p11 causes a dramatic reduction in their invasive potential. Why p11 is important for cancer cells is simply because p11 regulates the production and activity of proteases. The latter are involved in breaking physiological barriers surrounding cancer cells allowing them to invade and “metastasize”.

To date, the role of p11 in pancreatic cancer is not established. It is known that human pancreatic cancers have elevated levels of p11 potentially providing a needed advantage for this cancer. Supported by our previous work on p11 and by promising preliminary results, we propose that p11 plays an important role in maintaining cancer growth and metastasis in pancreatic cancer. For this purpose, we will be utilizing cellular and molecular approaches to study how p11 regulates protease activity and contributes to the invasive potential of pancreatic cancer cells. We will also utilize a unique mouse model which closely mimics human pancreatic cancer to better define the contribution of p11. It will ultimately help us define if p11 is a “druggable” target for metastasis-preventing treatments.

Project #4

Funded by: Partnership between Canadian Cancer Society Research Institute, New Brunswick Health Research Foundation and Craig’s Cause Pancreatic Cancer Society

Project Title: "Use of a Novel Extracellular Microvesicle Capture Method for the Enrichment and Identification of Pancreatic Cancer Biomarkers"

Researchers: Stephen Lewis (click here for CV), Rodney Ouellette and Anirban Ghosh, Moncton-based Atlantic Cancer Research Institute

Budget: $197,500 (over 2 years)

Outline: A current challenge for the treatment of pancreatic cancer is its early detection in high-risk populations. We currently do not have effective screening methods that allow this disease to be consistently detected early enough to allow appropriate treatment and a chance at a cure. Although research has uncovered red-flags that indicate the presence of pancreatic cancer, called biomarkers, these flags cannot be detected faithfully enough to allow for confident early diagnosis. Moreover, testing for pancreatic biomarkers requires invasive techniques, like a biopsy. Our approach will apply our novel technology for the capture of small packages of information from the blood (called extracellular microvesicles) to the detection of existing pancreatic cancer biomarkers. We will also use our technology to discover new, better biomarkers for pancreatic cancer. Our research will indicate if extracellular microvesicles represent a better way to detect pancreatic cancer at its earliest stages.

The development of better biomarkers for detecting pancreatic cancer at its earliest stage in high-risk populations will allow us to detect this disease when the best chance at a cure is possible. Indeed, surgical removal of the pancreas or the pancreatic tumor provides the best change for patient survival, but this needs to be done when the tumor is small and before it has spread to other parts of the body. Our approach will improve the efficacy of existing pancreatic cancer biomarkers and allow the development of new and better pancreatic cancer biomarkers for screening high-risk populations in a minimally-invasive manner.

This projects work is aimed at identifying biomarkers, or clues, in the patients’ microvesicles that could indicate accurately the existence of pancreatic cancer in somebody’s body much earlier than today’s conventional methods. If this happens, it could offer doctors a new, minimally invasive, effective way to detect pancreatic cancer early, especially with people who have an elevated risk for the disease.

The funding will be provided through the Canadian Cancer Society Research Institute’s Innovation Grants program, which was created to help scientists explore unconventional concepts within cancer research.

Project #5

Funded by: Cancer Research Training Program (CRTP) Award, Partnership between Beatrice Hunter Cancer Research Institute and Craig’s Cause Pancreatic Cancer Society

Project Title: “Understanding the roles of CTP Synthase and gemcitabine in pancreatic cancer”

Researcher: Gregory McCluskey (Supervisor, Dr. Stephen L. Bearne, Head of the Department of Biochemistry and Molecular Biology, cross-appointed with the Department of Chemistry)

Budget: $17,850 (per annum)

Outline: Research in the Bearne Lab focuses on developing a better understanding of how enzymes of therapeutic interest mediate cellular activities, and how they interact with chemotherapeutic agents. Specifically, the research examines the interaction of the drug gemcitabine with the chemotherapy target cytidine 5′- triphosphate synthase (CTPS). Information gained from these studies helps determine how gemcitabine inhibits CTPS and mediates its tumour-killing effects, and provides insight into how to overcome acquired chemoresistance.

Although pancreatic cancer is less common than other cancers, it is the fourth leading cause of cancer death amongst Canadians due to its low survival rate. Gemcitabine is a frontline chemotherapy agent used against pancreatic cancer. Although several enzyme targets for this drug have been identified, its interaction with the chemotherapeutic target CTPS is not well understood. CTPS promotes the formation of cytidine 5′-triphosphate (CTP), an essential building block for genetic material and biomembranes required for cell survival and division. CTPS is highly expressed in cancer tissues allowing tumour cells to multiply more rapidly. Gemcitabine closely resembles the molecules that CTPS normally interacts with and my preliminary data show, for the first time, that CTPS is directly inhibited by this drug. My research focuses on understanding how this drug inhibits CTPS and how resistance to this drug arises. These studies will be significant because they will inform future drug design and strategies for overcoming resistance to gemcitabine, which often occurs with pancreatic cancer.

Project #6

Funded by: Canadian Cancer Society, Craig’s Cause Pancreatic Cancer Society, National Pancreatic Cancer Foundation, QEII Foundation

Project Title: Could a vaccine prevent cancer from spreading after surgery?

Researcher: Dr Rebecca Auer, scientist and surgical oncologist at the Ottawa Hospital Research Institute (click here for bio)

Budget: $450,000

Outline: The main treatment for many types of cancer is surgery. In fact, more than half of all people with cancer will have some type of surgery to remove as much of the tumour as possible. But it can be challenging to find and remove all cancer cells. Unfortunately, sometimes cancer is more likely to spread after surgery, which is the problem that Dr Auer is addressing for pancreatic cancer.

The trauma of surgery can weaken the immune system, rendering it less able to detect and destroy any leftover cancer cells. “The immune system is in a constant battle with the cancer,” says Dr Auer. “While surgery itself does not cause cancer to spread, it can lower immunity, giving any residual cancer cells a fighting chance to grow back and spread.”

Currently there is nothing being done routinely to boost a patient’s immune system to prevent cancer from spreading after surgery.

To tackle this problem, Dr Auer has developed a vaccine containing oncolytic (or cancer-killing) viruses. This type of vaccine is intended to outsmart cancer cells, which often trick the immune system and escape detection. Oncolytic viruses are designed to safely travel through the body to seek out and destroy cancer cells while leaving normal cells intact. At the same time, the viruses can be engineered to strengthen the immune system to mount a powerful attack on cancer cells. It is this 2-pronged approach that makes the vaccine so promising.

Dr Auer has chosen to focus her research on pancreatic cancer because, despite surgical removal, the cancer almost always comes back, leading to one of the lowest survival rates of any cancer. She is hopeful that her research will lead to new therapies within as little as 5 years. “It seems far-fetched, I know, to use viruses to fight cancer, but I believe there will be a paradigm shift soon,” she says. Patients treated with oncolytic viruses typically experience very few and mild flu-like side effects, she notes, compared with traditional chemotherapies.

“We are elated to support Dr Auer’s work. This research will not only offer patients enhanced treatment options, it will provide patients with hope. Hope is a powerful tool for those faced with a pancreatic cancer diagnosis. We believe that pancreatic cancer research, such as Dr Auer’s, can and will alter pancreatic cancer outcomes in the near future,” says Stefanie Condon-Oldreive, founder, Craig’s Cause Pancreatic Cancer Society.

Dr Auer’s research was made possible by an Innovation to Impact Grant from the Canadian Cancer Society. The Society funds only the most promising projects with the greatest potential for impact through its gold-standard review process renowned in Canada and worldwide.

“There’s an urgent need to change the outlook for pancreatic and other hard-to-treat cancers,” says Dr Siân Bevan, director of research at the Canadian Cancer Society. “Investing in excellent Canadian science with our committed partners is allowing us to have a greater impact on pancreatic cancer survival rates sooner.”

-content from Canadian Cancer Society Press Release 2015



Project #7

Funded By: Craig’s Cause Pancreatic Cancer Society and Beatrice Hunter Research Institute

Project Title: Combined VSV and NKT cell activation in Panc-02 pancreatic cancer

Researcher: Adam Nelson, Masters Student, Dalhousie University

Project Cost: $17, 850

Outline: Pancreatic cancer is one of the deadliest cancers with a five-year survival rate of less than 4-9 %. The current treatments for pancreatic cancer are ineffective and have harmful effects on the patient. Therefore, new treatments that are safe and effective are urgently needed. One possibility is educating the immune system to fight pancreatic cancer.

Our lab is focused on developing strategies to educate the immune system to find and kill cancer cells. We focus on expanding and activating the population of Natural Killer T cell (NKT cells). NKT cells are potent anti-tumor immune cells that have been shown to be effective at killing tumor cells. Our lab has already demonstrated that increasing NKT cell populations is an effective treatment in breast cancer.

My project is focused on combining activation of natural killer T (NKT) cells with viruses that specifically target tumor cells called oncolytic viruses. The oncolytic virus I am working with is known as Vesicular Stomatitis Virus or VSV. I am also currently working on creating VSV strains that express various cytokines that will increase the NKT cells anti-tumor immune response and lead to increase tumor death. These studies are important because they provide a novel therapeutic route for cancer patients with less side effects than traditional treatment options.

Project #8

Funded By: Craig’s Cause Pancreatic Cancer Society and Beatrice Hunter Research Institute

Project Title: Repurposing anti-folate receptor antibodies for NK-driven precision pancreatic cancer immunotherapy

Researcher:  Helmi Alfarra, Post-Doctorate Student, Dalhousie University

Project Cost:  $73, 500 over two years

Outline:  Some cancers, but not healthy cells, overexpress a protein called folate receptor alpha(FRa), which can act as a flag for the immune system. Pancreatic cancer is highly deadly, and current cancer treatment approaches do not work well for pancreatic cancer. We know that some pancreatic cancers express the FRa “flag”, and we are trying to determine how to use it to teach the immune system to target them. Among all of the white blood cells that make up the immune system, we thing that one in particular, called the natural killer (NK) cell will be the best at killing cancer cells tagged for killing because NK cells specialize in recognizing this signal. In healthy people, NK defend the body from infections and cancer. They can tell the difference between healthy and normal cells by sensing signals for “self”. In cancer, this can be a problem because the tumour masks itself as a healthy cell. Therefore, in addition to “flagging” pancreatic tumours for killing by NK cells, it will be important to make sure that NK cells are not prevented from killing the tumour by signals that tell them to stop. In this study I will measure how well NK cells from different people kill pancreatic tumours expressing FRa and tagged for killing. I will watch to see what the characteristics for “good” and “bad” NK cells in the hope of designing new and effective strategies to treat patients with pancreatic cancer.

Project #9

Funded By: Craig’s Cause Pancreatic Cancer Society, Institute of Cancer Research, Canadian Institute for Health Research and Canadian Cancer Society

Project Title: Development of natural killer cell–based precision immunotherapy for pancreatic cancer

Researcher: Dr. Jeanette Boudreau, Canadian Cancer Society, Dalhousie University

Project Cost: $196,000 over two years


Each person with pancreatic cancer has a unique tumour, but each person has a unique immune system too. Dr Jeanette Boudreau and her team are studying how the immune system and the tumour interact, work together and oppose each other in order to decide whether the tumour will continue to grow or be eliminated by the immune system. Dr Boudreau plans to use this information to teach every pancreatic cancer patient’s immune system to effectively eliminate their tumour.

Pancreatic cancer has a poor survival rate because the tumour often remains undetected before it spreads to other tissues or it regrows after surgical removal. The immune system can be used to find tumours hiding throughout the body, and the researchers expect that this could be a good approach to treat pancreatic cancer. However, methods to accomplish this have not yet been developed. Dr Boudreau studies a type of immune cell called the natural killer (NK) cell, which is known to be good at controlling cancer. Researchers lack the detailed knowledge needed to precisely deploy NK cells against cancer. The team will be building on their previous work, where they developed technology to analyze NK cell function in greater detail than was previously possible. They showed how NK cell function is programmed in different people based on the genes they carry. In this project, the researchers will use model systems to develop and test a method for matching NK cells to tumours in a way that best facilitates their killing, toward the goal of developing immunotherapies for pancreatic cancer.

Immunotherapy is a promising new way to treat cancer. In immunotherapy, a person’s immune system is used to stop their cancer. Unfortunately, immunotherapy is challenging to apply because every tumour is different. Moreover, it has not been developed yet for pancreatic cancer, where treatment options are limited and survival is poor. The team thinks that natural killer (NK) cells could be ideal to exploit as a new kind of immunotherapy that could be made available to all people with pancreatic cancer. They will study how NK cells interact with pancreatic cancer to learn how to predict when and how they lead to tumour killing. Using lab experiments, genetic studies and computer analyses, they will figure out how to predict which NK cells are the best for each person’s individual pancreatic tumour. They will test how different NK cells kill tumour cells in order to build a computer program that selects the best NK cells for each person. They will also test its accuracy using a new mouse model of pancreatic cancer.

Mortality is decreasing among many types of cancer, but for pancreatic cancer, 5 year survival remains at less than 10%. With an expected increase in pancreatic cancer incidence, there is an urgent need for improved approaches to treating this disease. The researchers are developing NK cell–based immunotherapies for cancer. Natural killer cells have several properties that make them good for immunotherapy, including being able to use cells isolated from third party donors that are grown in the lab. The function of NK cells is controlled by many signals that are triggered by proteins on target cells, including cancer cells. The number of signaling triggers is limited. By studying their role in NK activation, the researchers expect to be able to design personalized immunotherapies to treat people with pancreatic tumours.

Project #10

Funded By: Craig’s Cause Pancreatic Cancer Society, Institute of Cancer Research, Canadian Institute for Health Research and Canadian Cancer Society

Project Title: Direct inhibition of mRNA translation for treatment of pancreatic cancer

Researcher: Dr. Michael Pollack, Canadian Cancer Society, Lady Davis Institute

Project Cost: $192,080 over two years


In this project, Dr Michael Pollak and his team will evaluate a novel approach to the treatment of advanced pancreatic cancer, a disease where current treatment options are limited. They will evaluate a new drug candidate that they expect will selectively block the synthesis of particular proteins that are required by cancer cells to behave aggressively. This approach has not previously been evaluated in pancreatic cancer in the lab, so they have established a collaboration that will allow them to test the drug candidate in a mouse model that closely resembles the human disease. They will gain insight into this therapy not only by monitoring tumour growth rates, but also the synthesis of the proteins that they expect will be influenced by the drug.

It is known that, in order to behave aggressively, cancer cells need to synthesize certain proteins that affect the control of their ability to multiply. The synthesis of these proteins requires specific processes that the researchers have discovered can be directly inhibited by a class of compounds that deserve evaluation as drug candidates. However, cancer cells can become resistant to many members of this class of chemicals simply by pumping them out of cells. The research team’s novel drug candidate has a structure that is resistant to this pumping‑out process, so it has a better chance of staying in the cell and being effective. However, it has not yet been evaluated in preclinical models of pancreatic cancer in the lab.

The researchers have identified a drug candidate that has the ability to block the synthesis of proteins required for aggressive cell behaviour when tested in cancer cells growing in plastic dishes in the lab. The objective of this study is to measure the ability of this chemical to inhibit the growth of pancreatic cancer in a well‑described mouse model and to determine if this is linked to the drug’s ability to inhibit the synthesis of proteins that are required by cancer cells to behave aggressively. The mice being used in this study will spontaneously develop pancreatic cancers that resemble the human disease. The researchers will compare the growth of cancers in untreated mice to mice treated with the drug, by monitoring the growth rate using ultrasound measurements and comparing the size and weight of tumours between groups at the end of the experiment.

Current treatments for advanced pancreatic cancer are inadequate, and most patients with this cancer have a very short survival period. This justifies research into novel therapeutic strategies. This project involves the preclinical evaluation of such a novel strategy – specifically the use of a drug candidate that directly inhibits the synthesis of proteins needed for cancers to behave aggressively – in a mouse model of pancreatic cancer. If the drug slows tumour growth in this model, the researchers will be in a position to move quickly into clinical trials, which may reveal a therapeutic benefit for patients. Furthermore, such a finding would motivate further research of this novel therapeutic approach for other cancers.



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