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Archive for the ‘Research News’ Category

Determining how proteins interact with breast cancer cells

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Hello, everyone! My name is Sami Khan and I’m an MSc candidate in the Department of Anatomy and Cell Biology at Western University. In Dr. Alison Allan’s laboratory at the London Regional Cancer Program, we study proteins that may be involved in the preferential metastasis (or spread) of breast cancer to the lung and the potential of these proteins to be used as targets for novel breast cancer therapies.

Sami Khan - Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit (TBCRU) scholarship recipienI am specifically interested in a family of proteins called selectins, which are normally found in the lung. Together with fellow lab members, we have demonstrated that the selectins enhance the migration or movement of breast cancer cells towards the lung. We are now in the process of determining the mechanism by which selectins interact with breast cancer cells and exert their function. Learning this will better enable us to develop strategies that can limit the spread of breast cancer cells to the lung and ultimately limit lung metastasis. These translatable findings could then be used clinically to improve breast cancer patient outcomes.

Without the funding support from the Breast Cancer Society of Canada, our research would not have been possible. As I finish up my MSc thesis, I am thankful for all the opportunities I was afforded and strongly believe that continued support from BCSC and its generous donors to researchers and trainees will lead to a breakthrough in breast cancer therapy one day soon.

Sami Khan, MSc Candidate

Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Support researchers like Sami and others by considering a donation to the Breast Cancer Society of Canada. Find out how you can help fund life-saving research, visit bcsc.ca/donate

 

Investigating early events in estrogen signaling

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Hi, my name is Bart Kolendowski and I am a PhD candidate in the Department of Biochemistry at Western University. I currently work at the London Regional Cancer Program in Dr. Joe Torchia’s lab researching the role of the estrogen receptor in breast cancer.

The estrogen receptor is often a therapeutic target in a subset of breast cancers. My work has focused on investigating early events in estrogen signaling to better understand how therapies work and, more importantly, why they sometimes fail.

Bart-Kolendowski - BCSC - Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit (TBCRU) scholarship recipientDuring my tenure as a Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit (TBCRU) scholarship recipient, I have discovered previously unknown mechanisms that drive estrogen-dependent breast cancer. Importantly, these discoveries have led to the identification of new targets that may prove to be of therapeutic value for patients suffering from breast cancer.

I have been invited to present this work at the Canadian Institutes of Health Research National Student Research Competition held at the University of Winnipeg as well as the prestigious Keystone Symposia on Nuclear Receptors held in Snowbird, Utah.

Earlier this year, we submitted a manuscript based on my findings to a high-impact academic journal for publication. I am happy to announce that we are currently in the process of completing revisions and anticipate that the work will be published in the upcoming months!

None of this would have been possible without the continued support of the TBCRU and the Breast Cancer Society of Canada.

Thank you!

Support researchers like Bart and others by considering a donation to the Breast Cancer Society of Canada. Find out how you can help fund life-saving research, visit bcsc.ca/donate

What being a breast cancer researcher has taught me.

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Hello! My name is Ashkan Sadri and I’m a Masters candidate in Dr. Alison Allan’s lab in the Department of Anatomy and Cell Biology at Western University, just coming to the conclusion of my thesis research.

When I engage in casual conversation, the topic of graduate school and breast cancer research often arise. By far, the most common question I’m asked is: “Does a cure exist?” And to that, it’s hard to give a simple answer.

Ashkan Sadri, BCSC ResearcherWhat is difficult to communicate to those outside of the cancer research field is that, due to the complexity of cancer, it is unlikely a single cure exists. Over the past two years, the basis of my research has been to investigate whether the factors produced by different organs in the body such as bones and the lungs can promote a rare, stem-like population of breast cancer cells with heightened capacity to form metastatic tumors in these organs. Our research findings turned out to challenge our predictions, providing an important means for thinking outside of the box. Not only were the stem-like traits of breast cancer cells not promoted when exposed to the lung microenvironment, they were actually reduced. We have gone on to identify a novel subpopulation of breast cancer cells that may potentially be involved in metastasis to the lung, using pathways that are distinct from the original cancer stem cell model. Thus, when asked, about a “cure to cancer”, it’s important to consider the complex nature of cancer biology and the many unknowns that exist, emphasizing the need for valuable research to be conducted.

When confronted with a treatment, breast cancer cells often find alternative means to progress along their path. Cancer treatments are effective in blocking key pathways, but alternative routes exist that the cancer cells can utilize. This is why supporting breast cancer research is vital. Learning about different mechanisms that drive tumour development are necessary to finally get breast cancer under control. By supporting breast cancer research, researchers are able to make a global impact when it comes to gaining ground on cancer.

Thank you to BCSC for your trainee support!

– Ashkan Sadri

Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

Support researchers like Ashkan and others by considering a donation to the Breast Cancer Society of Canada. Find out how you can help fund life-saving research, visit bcsc.ca/donate

 

“Research is a shared responsibility of participants and investigators”

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Becky S., 37, calls herself “a girl on a winning streak.” That might sound a bit strange after you learn that she is a breast cancer survivor who has had an extensive history of surgery and chemotherapy. Yet, Becky truly believes that her hormone-sensitive stage II breast cancer, which was diagnosed in 2016, has been a stroke of luck, unlike other forms of the disease. “With my particular type of cancer, I seem to be eligible to participate in a clinical trial to become pregnant. I must take tamoxifen for five years. Hopefully the trial will give me a chance to have a baby safer.”

It has long been thought that pregnancy increases the probability of breast cancer relapse and the appearance of distant metastases, especially for women with estrogen-positive (ER+) disease. Estrogen plays a significant role during pregnancy, but it also provokes ER+ cancer cells growth and can awaken cancer cells that remain in the body even after the heavy treatment.

Clinical Trials Word CloudYet, findings from a multicenter retrospective study show that for women with a history of ER+ breast cancer, pregnancy can be safe. The findings of the study were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by lead study author Dr. Matteo Lambertini (the Jules Bordet Institute in Brussels, Belgium).

Just a year ago, Becky had never heard words like “retrospective study” or “clinical trials”.  Her immersion in the field of breast cancer research unfolded gradually after a casual chat with her co-worker Lizzy at a party last year. Lizzy’s grandmother died of breast cancer many years ago, when tamoxifen was not available. The only option for endocrine therapy for women with ER+ breast cancer was oophorectomy, i.e. ovary removal. This procedure left women unable to have any biological children.

“Lizzy told me – Hey, you keep your ovaries inside, so technically you can have a baby! Science is constantly evolving. Just ask your doctor about the options for you,” recalls Becky. “Lizzy’s words firmly caught my mind. But my husband said pregnancy may be dangerous. He said, ‘I don’t need a child in exchange for your life.’”

Undeterred, Becky began searching for information on pregnancy after breast cancer treatment. She faced a lot of controversial opinions and specific medical terms. “I’ve read through so many specialised websites that I consider myself a kind of a self-taught researcher,” says Becky with a smile. Now, she confidently differentiates randomised controlled studies from, say, meta-analyses and reads a PubMed without having to double-check what a P-value is.

“It is not that overwhelming. Rather, the opposite, in fact. I would recommend all cancer survivors to be aware of what is going on in the field. Since I started learning more about cancer research, I feel calmer and a bit more protected. I see how hard researchers work on a cancer cure and how much has already been done to fight breast cancer. It’s highly supportive.”

Recently, Becky heard about The POSITIVE study that will research breast cancer and pregnancy. This study will evaluate the pregnancy outcomes and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who wish to become pregnant. In other words, the goal of this study is to assess whether it is safe for breast cancer survivors to temporarily stop taking their hormone blockers such as tamoxifen and aromatase inhibitors, which are normally recommended for 5-10 years after initial treatment and may be dangerous for a fetus. The study also aims to evaluate different specific indicators related to fertility, pregnancy and breast cancer biology in young women.

Becky S Quote

“This study is exactly what I need,” says Becky. “I believe it is my chance to both become a mother and show other women that hormone-positive breast cancer is no longer a sentence to childlessness.”

Participants will put endocrine therapy on hold for up to two years to enable pregnancy, delivery and breast-feeding. Then, therapy will be resumed. Participants will also be followed for 10 years after enrollment in the study. More information about the POSITIVE study can be found on ClinicalTrials.gov (Registration # NCT02308085).

The good news is that The POSITIVE is currently active in Canada. I met with Becky at Sunnybrook Health Sciences Centre, one of the participating institutions, where she came to learn more about the study. As a curious patient, she has already familiarized herself with all the details available on the Internet and compiled a list of questions to ask a clinical trials professional.

“Clinical trials and research are a shared responsibility of participants and investigators,” says Becky. “Some folks who are aware of my plan told me that I will be a kind of guinea pig, but they are completely wrong. I will become a teammate with a very special role, and hopefully I will become a mother some day despite the breast cancer in my past.

Natalia Mukhina –
Health journalist, reporter and cancer research advocate

Natalia Mukhina - Health Journalist

Natalia Mukhina, MA in Health Studies, is a health journalist, reporter and cancer research advocate with a special focus on breast cancer. She is blogging on the up-to-date diagnostic and treatment opportunities, pharmaceutical developments, clinical trials, research methods, and medical advancements in breast cancer. Natalia participated in numerous breast cancer conferences including 18th Patient Advocate Program at 38th San Antonio Breast Cancer Symposium. She is a member of The Association of Health Care Journalists (AHCJ).

Uncovering the role of RNA in breast cancer

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My name is Thomas Huynh and I’m a Masters student in Dr. Paola Marcato’s laboratory in the Department of Pathology at Dalhousie University. The support generously provided to me by the Breast Cancer Society of Canada and the QEII foundation through the Beatrice Hunter Cancer Research Institute has been invaluable in helping me pursue my research goals.

Thomas Huynh BCSC ResearcherWorking with Dejan Vidovic, a fellow graduate student in Dr. Marcato’s laboratory, our work focuses on uncovering the role of a long non-coding RNA (lncRNA) discovered by Dejan in breast cancer disease. Previously dismissed as “genomic junk”, evidence is emerging that lncRNAs play a pivotal role in the development, progression and pathology of breast cancer. Our work shows that the lncRNA RAINR has an oncogenic role in breast cancer. Employing a variety of molecular technologies, we observed that knocking down expression of RAINR dramatically increases the apoptosis of breast cancer cells and decreases their proliferation, indicating its importance in disease development. We are now working towards characterizing the mechanisms behind RAINR function. This could potentially uncover a new therapeutic target for the treatment of breast cancer.

I am extremely grateful for the support provided to me for this project, as well as other opportunities to expand my graduate experience. I was afforded the opportunity to attend an international cancer conference in Florence, Italy to share my work with other high caliber researchers and was recently awarded the inaugural CRTP Collaboration Grant to start a new project studying the treatment of a subtype of leukemia in collaboration with Dr. Ian Weaver’s research group at Dalhousie University.

Thank you once again BCSC as well as the BHCRI and the QEII Foundation for your ongoing support,

Thomas Huynh

3D Surface Imaging Technique for Breast Cancer

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My name is Olivia Tong and I am a MESc candidate in the Department of Biomedical Engineering under Drs. Jeffrey Carson and Mamadou Diop at Lawson Health Research Institute.

BCSC Researcher - Olivia Tong - 3D Surface Imaging Technique for Breast CancerWe are developing a non-contact scanner that can monitor the blood oxygen level in the tumor during chemotherapy. The success of this project will lead to a new diagnostic method that can quickly identify the most effective chemotherapy drug for each breast cancer patient. You might have seen Lawrence Yip’s blog posts regarding Photoacoustic Imaging Research. For this scanner, we also use photoacoustic imaging to detect breast tumors. As an improvement, we are building a non-contact system. I am working on a component of this non-contact scanner that captures the 3D shape of the breast using 3D surface imaging technique. The 3D information of the breast is important for reconstructing the photoacoustic images collected by the other component of the scanner.

The support of TBCRU enabled me to purchase a commercial structured light scanner for the development of my system. My next step is to evaluate the performance of my system on a small group of human subjects before integrating my component into the non-contact scanner. For this project, we also collaborate closely with clinicians at the breast cancer center at St. Joseph’s Hospital and researchers at McMaster University.

This May, I have the opportunity to meet with our collaborators and learn more about biomedical optics. I am very grateful to be supported by TBCRU and work for this amazing project.

Finding a Novel Strategy to Prevent Metastasis

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“What my patients with early stage breast cancer really fear is to hear the word ‘metastasis’.” Most oncologists would agree with this statement, which I once heard from a presenter at the San Antonio Breast Cancer Symposium.  There is no doubt that being told you have metastatic breast cancer is a lot to take in, as it means that breast cancer has spread beyond the breast to other parts in the body. The disease becomes more advanced the farther it spreads. And, unfortunately, it also becomes incurable.

How can the appearance of metastases be prevented? One of the ways to address this issue – and probably the most promising – originates from the field of molecular biology and biochemistry.

Dr. Jean-François Côté, Director of the Cancer and Genetic Diseases Division in MontrealDr. Jean-François Côté Clinical Research Institute (IRCM), explores the molecular signals that allow cancer cells to seed and grow new tumors, and how to stop this spread. Along with his research team, he looks at signalling pathways that control cell migration. One of the team’s current projects focuses on breast cancer. Recently, Dr. Côté visited the Cancer Research Institute at Queen’s University and shared details of this research during a seminar titled “Unravelling the complexity of metastasis: Characterizing the roles of the receptor tyrosine kinase AXL in metastatic progression.”

What is the research agenda of Dr. Côté’s team? Statistics indicate that the majority of breast cancer deaths occur because of the manifestation of metastases. The metastatic process is complex: cancer cells detach from a primary tumour, enter nearby blood vessels, and migrate in the vascular system. Throughout this process, cancer cells exchange signals, and such signaling pathways drive tumor progression and metastasis after cancer cells reach and survive at secondary sites.

In a nutshell, AXL is a cell surface receptor. As Dr. Côté explains, the expression of AXL correlates with the appearance of metastases in several types of cancers, including breast cancer. AXL stimulates cell proliferation promoting cell survival, resistance, invasion, and metastasis. In other words, signals from AXL help malignant cells grow and spread to distant areas in the body.

A snapshot of AXL cooperating with HER2 in human breast cancer samples

A snapshot of AXL cooperating with HER2 in human breast cancer samples

The mechanism AXL uses to perform its pro-metastatic role is still not completely clear. To identify signaling networks controlled by AXL, Dr. Côté borrowed proteomics approaches – protein-based analysis methods that help estimate the relative and absolute amounts of thousands of proteins across diverse biological systems. Proteomic technologies are in high demand in cancer studies as they have the potential to lead to the discovery of new therapeutic targets and improve the precision of anti-cancer treatments.

What unites researchers in the cancer field all over the world is the understanding that a “one-size-fits-all” strategy for treating cancer no longer works. We live in the era of a tailor-made individualised approach. Searching for ways to personalize breast cancer treatment is considered the most promising way forward for leading cancer researchers. As researchers such as Dr. Côté and his team learn more about the molecular mechanisms controlling signaling by the receptor tyrosine kinase AXL, they are better able to move forward and identify some pharmacologic targets for treating breast cancer. The next major step will be designing novel anti-cancer therapies that will work better than conventional untargeted chemotherapy. “Old-school” chemotherapy kills without distinction. Targeted drugs attack breast cancer without harming benign cells.

Dr. Côté also employs in vivo approaches. In vivo (Latin for “within the living”) means that an investigator uses a whole, living organism in research. Regarding cancer studies, in vivo testing involves mouse models and human patient-derived xenografts. In the case of xenografts, human tumor cells are transplanted into a mouse. This allows the design of a model with the same biological parameters as an actual cancer patient. Obviously, this is a perfect way to observe the overall effect of an experiment using a living subject, while not harming people.

Much has been achieved in research and much more remains to be done, as Dr. Côté says. To date, findings indicate that the receptor tyrosine kinase AXL is a promising therapeutic target for breast cancer therapy. “Our results suggest that inhibition of AXL would be beneficial in limiting the spread of breast cancer,” argues Dr. Côté.

Natalia Mukhina –
Health journalist, reporter and cancer research advocate

 

Natalia Mukhina - Health Journalist

Natalia Mukhina, MA in Health Studies, is a health journalist, reporter and cancer research advocate with a special focus on breast cancer. She is blogging on the up-to-date diagnostic and treatment opportunities, pharmaceutical developments, clinical trials, research methods, and medical advancements in breast cancer. Natalia participated in numerous breast cancer conferences including 18th Patient Advocate Program at 38th San Antonio Breast Cancer Symposium. She is a member of The Association of Health Care Journalists (AHCJ).