Author Archives: torontoriot

Can a Genetic Test Help Personalize Prostate Cancer Treatment for Men?

By: Joseph Longo

PCa BRCA2 Blog Image.jpg

Prostate cancer is the most commonly diagnosed cancer among Canadian men, with 1 in 8 men expected to develop the disease in their lifetime. Thanks to advances in early detection and screening, prostate cancer treatments have significantly improved over the years and, if caught early, the 5-year survival rate is nearly 100%. Despite these advancements, over 4000 men still die of prostate cancer each year, making it the third-leading cause of cancer-related death in men.

Treatment for prostate cancer can vary depending on the stage of the disease at diagnosis and how likely the disease is to grow and spread to other parts of the body. Men diagnosed with low-risk prostate cancer tend to go on ‘active surveillance’, where regular check-ups and testing are recommended to closely monitor disease progression. This avoids the need for invasive and aggressive therapies with unwanted side effects in patients with small, slow-growing and asymptomatic disease. Men at higher risk of disease progression are treated with a combination of surgery, radiation therapy and/or hormone therapy. While these lines of therapy are initially effective, approximately one-third of patients will have their cancer return in a more aggressive and lethal form. We currently do not understand why some patients respond to these forms of therapy, while others do not. If we can predict treatment failure, then we can spare patients from unnecessary and ineffective treatments, and potentially offer more personalized and effective treatment options at diagnosis.

A recent study led by a team of researchers from Toronto and Melbourne found that prostate cancer patients with an inherited mutation in the BRCA2 gene tend to have more aggressive and advanced forms of the disease. Mutations in the BRCA2 gene, and its relative BRCA1, are typically associated with an increased risk of breast and ovarian cancers. You may remember the news headlines from 2013 when actress Angelina Jolie underwent a preventative double mastectomy after testing positive for a BRCA1 mutation. What people are less aware of, however, is that inherited mutations in the BRCA2 gene also increase the risk of developing prostate cancer. BRCA1 and BRCA2 are important players in the cell’s ability to repair damage to its DNA. When mutations in these genes prevent them from working properly, it increases the chances of developing cancer.

Prostate tumours in men with an inherited mutation in BRCA2 tend to be more aggressive and have a higher chance of spreading to other parts of the body. These patients are also more likely not to respond to first-line prostate cancer treatments, including surgery and radiation therapy. While the chances of having an inherited BRCA2 mutation are low (less than 1% of the population), testing for this mutation at diagnosis could spare men who are mutant BRCA2-positive from going through therapies that are likely to fail. Instead, these patients may benefit from more aggressive treatment upfront, including chemo- and targeted drug therapies.

This article was written by Joseph Longo. Joseph is currently pursuing a PhD in the Department of Medical Biophysics at the University of Toronto. He studies how statins can be used to treat cancer. To learn more about Joseph and his research, check out our members page.

References

  1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2016. Toronto, ON: Canadian Cancer Society; 2016.
  2. Taylor et al., 2017. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nature Communications. doi: 10.1038/ncomms13671.

Drug Repurposing for Colorectal Cancer: Redesigning a House Into a Bookstore

By: Douglas Chung

repurposing-drugs-bookstore-dc

What if there was a quicker and cheaper way to bring forth more treatment options for people with cancer? Researchers are trying to do just that by repurposing drugs used for other diseases to treat cancer.

The process of drug development is a costly and lengthy process. Candidate drugs must undergo multiple stages of research and evaluation before they meet the safety and therapeutic requirements to be routinely used in the clinic.

Similar to building a new house, the drug development process requires a novel structural design, construction, and passing of safety regulations. However, once the house is built, it can often be repurposed for different uses including a bookstore, restaurant or dance studio.

Similarly, some approved drugs could be repurposed to treat other diseases than what they were originally intended for. Drug repurposing has gained a lot of interest within the cancer field. The advantage of this approach is that the initial research on how the drug works in the body and its potential side effects have already been done. Drug repurposing dramatically reduces the cost and time it takes to introduce new therapies for cancer patients.

Cimetidine: A treatment for heartburn repurposed for cancer

Cimetidine is an anti-histamine drug used to treat heartburn and peptic ulcers. In 1988, researchers reported that patients with stomach cancer, who happened to be treated with cimetidine for heartburn, demonstrated tumour shrinkage and increased survival [1]. In the past decade, an abundance of animal and clinical trials have provided evidence suggesting that this drug may be a good potential therapy for cancer. But how does a heartburn medication work against cancer?

Cimetidine promotes immune cells to attack tumour

One of the ways cimetidine promotes tumour regression is by promoting immune cells to attack cancer cells. The cells of the immune system are the defenders of our body from not only foreign substances like bacteria and viruses, but also from our own cells that have gone awry. They are capable of recognizing cancerous cells, and subsequently coordinating an organized attack against the tumour.

The best way to describe the epic battle between the immune system and cancer, is to compare it to famous scene in Star Wars when the Death Star (tumour) was attacked by the Rebel Alliance’s X-wing Starfighters (immune cells). Tumours have defensive mechanisms (the Empire’s TIE fighters, or in this case myeloid-derived suppressor cells and regulatory T cells) to stop immune cells from attacking it. This allows the tumour to continue to grow without surveillance.

Several studies have shown that cimetidine targets and shuts down the suppressor cells (Empire TIE fighters) [2,3]. By shutting down suppressor cells, the immune cells are free to attack the tumour with the ultimate goal of destroying that Death Star.

Cimetidine in colorectal cancer

A number of clinical trials have shown promising results using cimetidine to treat colorectal cancer. In a 2002 trial, 64 colorectal cancer patients underwent surgery and were given 5-fluorouracil, a common chemotherapy given after surgery. [4]. Of these 64 patients, 34 patients also received daily doses of cimetidine for a year starting 2 weeks after surgery. Patients were followed for 10 years and those given cimetidine had a higher survival rate.

A recent review which analyzed results from 5 clinical trials, with a total of 421 patients with colorectal cancer (CRC), further confirmed the positive survival benefits of receiving this drug post-surgery [5].

Cimetidine has also shown promise in melanoma, gastric cancer, and renal cell carcinoma [6]. More clinical trials are ongoing to investigate if cimetidine may also provide benefits in other cancer types and whether this is due to the enhancement of the immune system. Time will tell whether this repurposed drug becomes a standard treatment option for colorectal cancer and other cancer types.

This article was written by Douglas Chung. Douglas is a research assistant working in Dr. Pamela Ohashi’s Lab at the Princess Margaret Cancer Centre where he studies how to use the immune system to fight cancer. To learn more about Douglas and his research check out our members page.

References:

  1. To̸nnesen H, Bulow S, Fischerman K, Hjortrup A, Pedersen V.M, Svendsen L, et al. Effect of cimetidine on survival after gastric cancer. The Lancet. 1988;332(8618):990-992.
  2. Zheng Y, Xu M, Li X, Jia J, Fan K, Lai G. Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Molecular Immunology. 2013;54(1):74-83.
  3. Zhang Y, Chen Z, Luo X, Wu B, Li B, Wang B. Cimetidine down-regulates stability of Foxp3 protein via Stub1 in Treg cells. Human Vaccines & Immunotherapeutics. 2016;12(10):2512-2518.
  4. Matsumoto S, Imaeda Y, Umemoto S, Kobayashi K, Suzuki H, Okamoto T. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. British Journal of Cancer. 2002;86(2):161-167.
  5. Deva S, Jameson M. Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer. [Internet]. 2012 [cited 8 February 2017]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007814.pub2/full
  6. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme V.P. Repurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent. ecancermedicalscience. 2014;8.

A ‘Big Bang’ Theory of Pancreatic Cancer Development

By: Kinjal Desai, Ph.D.

kinjal-blog-picture

Genetic changes causing pancreatic cancer occur all at once, like a big bang, due to massive genetic instability within the cell.

Relatively rare compared to more common cancers, pancreatic cancer is the fourth leading cause of cancer death in both women and men in Canada. Survival beyond 5 years is below 10%. What makes pancreatic cancer so deadly? In part, this is due to the appearance of disease symptoms when the cancer is already at a very advanced stage, despite many efforts toward an early detection. New research out of Toronto now explains why pancreatic cancer is so hard to detect early by providing insight into how it actually develops.

This recent study demonstrates that pancreatic cancer appears to develop spontaneously and rapidly following an event that causes the genome to become highly unstable, leading to thousands of genetic changes happening all at once. This is in stark contrast to the previous views on how cancer forms.

The previous theory is that cancer follows the principles of evolution much like what was identified by the great naturalist Charles Darwin. He proposed a theory of natural selection, that can be described in the following example: a bird has randomly acquired a DNA mutation that causes it to have a very long beak compared to other birds in its flock. Supposing there is a drought in the region and the only seeds available were buried deep in the ground, the once abnormal long-beaked bird now has the most advantage and survives, whereas the shorter-beaked birds in its flock are more vulnerable to starvation. When the long-beaked bird reproduces, it passes on its mutation and the long beak becomes more common or “selected” in the population. However, once the drought passes and long beaks are no longer beneficial to birds for survival, the mutation, offering no particular advantage, may start to once again become a minority in the population.

Darwin’s evolutionary model is frequently seen in cancers too. Cancer cells, which arise from normal cells, randomly acquire mutations in key genes that offer them a growth advantage. Every time a cell acquires a “cancerous” mutation, it gains greater power to grow faster and survive. These mutations, occurring randomly and in a stepwise fashion, eventually create a full-blown cancer.

But this new study from Toronto makes us rethink this theory when it comes to pancreatic cancer. It had previously been observed that pancreatic cancer becomes aggressive almost as soon as it begins forming. This new research suggests that the reason for this is that the disease-causing mutations may be occurring simultaneously with a “big bang” event, rather than in a gradual and stepwise fashion. The authors, led by a team based at the Ontario Institute of Cancer Research (OICR), used a computational method to track the genetic changes in over 100 pancreatic tumour samples to reach their conclusion.

They proposed that pancreatic cancer follows a model of evolution known as “punctuated equilibrium.” The theory was first proposed by Stephen Jay Gould and a colleague, Niles Eldredge, to refer to significant evolutionary changes that occur rapidly in spurts, and which are preceded and followed by long periods of slow and gradual changes described by Darwin’s natural selection. A similar process was also reported in colon cancer, and was referred to as a “big bang” model of cancer growth. This striking analogy is a powerful description of the rapidly changing state from normal to cancerous in certain cases.

This study offers an important new perspective to understanding cancer evolution. By more carefully identifying the different ways in which cancer can evolve in our bodies, researchers and clinicians can better design specific therapies to target them.

This article was written by Dr. Kinjal Desai. She is a postdoctoral research fellow at the Hospital for Sick Children in Toronto, where she works on medulloblastoma, the most commonly occurring malignant brain tumour in children. To learn more about Kinjal and her research check out our members page.

References:

Notta F., Chan-Seng-Yue M., Lemire M., Li Y., Wilson G.W., Connor A.A., Denroche R.E., Liang S-B., Brown A.M.K., Kim J.C., et al. A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538, 378–382 (20 October 2016) | doi:10.1038/nature19823

Sottoriva A., Kang H., Ma Z., Graham T.A., Salomon M.P., Zhao J., Marjoram P., Siegmund K., Press M.F., Shibata D. & Curtis C. A Big Bang model of human colorectal tumor growth. Nature Genetics 47, 209–216 (2015) | doi:10.1038/ng.3214

Darwin, C. On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. Nature (1859). London: John Murray, 5 (121): 502.

Eldredge, N., Gould, S.J. Punctuated equilibria: an alternative to phyletic gradualism. Models in Paleobiology (1972) pp 82-115.

 

Tackling the Fear of Cancer Recurrence: An Interview With Survivorship Researcher Dr. Christine Maheu

 

By: Sangeetha Paramathas

christine-maheu-image

Dr. Christine Maheu is an associate professor in the Ingram School of Nursing at McGill University as well as a FROS Junior 2 Research Scholar and a clinical scientist at the Princess Margaret Cancer Center. Her research is focused on cancer survivorship with particular interest in developing clinical interventions for fear of recurrence and a difficulty with going back to work.

How long have you been in the research field?

I started my PhD in 1998 and began conducting research in 1996 by being a research assistant at the master’s level.

What does your research focus on?

For my PhD at UBC, I interviewed 22 families who were testing inconclusive for the genes BRCA1 and BRCA2. They had a very strong family history of breast and ovarian cancer but they couldn’t find a mutation. I studied what the psychological impact is of knowing that you are at risk of developing cancer. For my post-doc at U of T, I developed an intervention to deal with the anxiety and the uncertainty that arises from living with an unknown inherited mutation for cancer. Afterwards, that study led me to the fear of cancer recurrence study for patients finishing cancer treatment. Fear of cancer recurrence is often the number one concern and is also often unscreened and untested. With a colleague from the University of Ottawa, Dr. Sophie Lebel, we put together an intervention – it is a 6-week therapy group, that was built from evidence and is theory based. It is a cognitive existential group therapy that is currently offered for breast and gynaecologic cancer survivors and is available in Montreal, Ottawa, and Toronto.

What is cognitive existential therapy?

It focuses on how to reframe your thoughts in such a way that the patients do not automatically feel that every pain, ache or bodily sensation is a sign of recurrence. We help them look at how to unfreeze themselves from their anxiety and what the impacts of living in constant worry are. We’re teaching them coping skills such as: reading, going out for a walk, doing relaxation exercises and calming self-talks. We teach them how to self assess so that they know when to use their coping skills and what method is more effective for them to lower their anxiety and fear of recurrence.

What does a typical workday, like today, look like for you?

I am involved in many studies. Right now, we are in the recruitment phase for three studies. I ensure that we have pamphlets and ads up for recruitment and I talk to physicians to see if they have patients to refer. I like to keep up-to-date on where we are with data collection and oversee data entry from questionnaires. I coordinate follow-ups with patients, prepare for presentations and talks and work on my own scientific papers. I also supervise graduate students!

What are the best and hardest parts of the therapeutic interventions that you run?

The last session of the 6-week intervention is what I look forward to the most. Realizing that we’ve made a difference in these women and that it has helped them. Rarely do I see that the work we do hasn’t made any change, and it is nice to see that.

The hardest part is helping patients go through difficult sessions (such as sessions 4 and 5) where they talk about their worst-case scenarios and having to discuss it. Often their fears are about “What happens if I pass away” and “What would happen to my family”.  These are difficult moments that we need to prepare for ourselves as group leaders to make sure that we are well grounded.

Why is survivorship research important?

All the late and long-term effects of cancer and its treatments are important. Often patients who have finished their treatment will tell you that they feel they are forgotten, that they still have questions, and wonder who will be following up with them. Cancer survivorship is a stage of the disease and cancer is a chronic illness that you have to live with; it’s not like catching a cold. We have to develop a program of care for these patients who will be feeling different (long-term) symptoms that require professional care.

Is integrating survivorship care into primary care important?

Once patients finish treatment, the transition to their primary care (family) physician is difficult; there is no streamlined approach. Some patients will get good follow-up care whereas others may not. Ideally, we would like for the family physicians to be involved with the patients cancer care from the start with the oncology team. Patients would gain from being informed early on of the possible late and long-term effects that may result from their cancer and cancer treatment, and these include the psychological impact. Survivorship care needs to be discussed at the start of treatment using a standardized approach, and perhaps one that is universal across all provinces. The issues with cancer and its treatment remains the same no matter what province you are from.

How has research in survivorship research changed since you started in research?

The psychological aspects of cancer care weren’t considered an issue 15-20 years ago. Now it is becoming more known and accepted that there is a psychological aspect to cancer care. Now, there are many organizations and conferences (such as the Canadian Association of Psychosocial Oncology (CAPO) for nurses, social workers, doctors, psychologists and psychiatrists to come together and discuss the psychosocial aspects of cancer. Distress and anxiety are becoming additional vital signs that are screened for as part of follow-up cancer care. Today, most provinces have in place a survivorship program or a wellness centre available to patients right from the beginning.

Thank you so much for your time Dr. Maheu. Your work sounds very important and it addresses key aspects of cancer care and illustrates cancer research in a new light. You are doing some amazing work, good luck!

This article was written by Sangeetha Paramathas. Sangeetha is currently a PhD candidate in the Department of Medical Biophysics at the University of Toronto. She studies how liquid biopsies can be used for cancer surveillance and diagnosis. To learn more about Sangeetha and her research, check out our members page.

Autophagy: a Fundamental Cellular Process That Goes Haywire in Cancer

By: Mike Pryszlak

mike-autophagy

Image: tumour cells exploit the autophagic process

The Nobel Prize, established by Alfred Nobel in 1895, is the highest award an individual can receive for their academic, cultural or scientific contributions.  Alfred was himself a chemist and inventor who amassed a fortune by inventing Nobel’s Blasting Powder, or dynamite, and subsequently became a major armaments manufacturer.  His invention changed the world- and although it revolutionized the mining, quarrying and construction industries, Nobel struggled with feelings of guilt as he realized the death and destruction he had brought upon society.  In his will, he established the Nobel Foundation with the mandate to use his wealth for the greater good by awarding a prize to individuals who “confer the greatest benefit on [human]kind” in physics, chemistry, physiology or medicine, literature and peace.

This year, the Nobel Prize for physiology or medicine was awarded to Dr. Yoshinori Ohsumi for his discoveries of the mechanisms for autophagy.  What is autophagy you may ask?  Turns out you are not alone- on the Nobel website, which typically attracts a highly scientific audience, 44% of people randomly polled had never heard of it before.  So what is so special about autophagy when hardly any one knows what it is? Let me explain why this research is so important and what it means for cancer.

Autophagy, also known as “self-eating”, is the controlled break down and recycling of cellular components, which is an essential part of a cell’s normal housekeeping duties.  Similar to an aquarium, a cell can be thought of as a closed ecosystem where only a limited amount of resources exist; they need to be preserved and reused.  Over time, cellular structures, both large and small, break down, get old or are damaged by normal wear and tear.  The cell recognizes they need to be replaced and sends a signal to begin the autophagic process by “fencing off” the target in a structure called an autophagosome, marking it for recycling.  The autophagosome then fuses with a lysosome, which is full of enzymes that can break down any biomolecule into its raw components.  These pieces can then be used as building blocks for new, or other cellular components.   Dr. Ohsumi was the first to identify the genes necessary for autophagy.  When they fail or go haywire, cells cannot functional normally and this is the root cause behind many diseases including cancer.

Cancer cells use autophagy in very unusual, abnormal ways.  The reasons behind “why?” or “how?” are very poorly understood, and are active areas of research.  What is really interesting, is that scientists have seen autophagy involved in both promoting and preventing cancer, depending on the stage of tumour development or the type of cancer.  In early stages, it can inhibit cancer growth by preventing the accumulation of any damaged proteins or structures, keeping cells healthy and happy.  In more advanced tumours, on the other hand, when faced with chemotherapy or radiotherapy, cancer cells deliberately use autophagy to cope with these stresses and to repair or replace any damaged structures.  Autophagy also allows cancer cells to keep producing energy to survive and grow in conditions where a normal cell wouldn’t stand a chance.  For example, in environments where cells have no access to nutrients to grow, cancer cells can recycle and re-direct their existing nutrients into pathways that allow them to survive and continue to grow. Fortunately, this process can be exploited to restore sensitivity to chemotherapy, increasing response to treatment, which makes it a highly promising and exciting area of research.  Just earlier this year, here in Toronto, the research group of Dr. Peter Dirks at SickKids Hospital showed that when dopamine (a signaling molecule in the brain) receptors are “turned off”, autophagosomes accumulate and contribute to the death of brain cancer stem cells.  This opens the door for new therapeutic strategies as this is typically a notoriously difficult population to target.

Despite that fact that most people haven’t heard of autophagy, the pioneering work of Dr. Yoshinori Ohsumi has massively advanced our understanding of both normal and cancer cell biology, opening up countless avenues of research.  As with all Nobel laureates, their legacy will impact generations to come.  Congratulations on winning the Nobel Prize, Dr. Ohsumi, and thank you.

This article was written by Mike Pryszlak. Mike is currently completing the fourth year of his PhD at the University of Toronto. He studies how normal stem cell genes are changed in cancer stem cells. To learn more about Mike and his research check out our members page.

References and further reading:

Dolma, S., Selvadurai, H.J., Lan, X., Lee, L., Kushida, M., Voisin, V., Whetstone, H., So, M., Aviv, T., Park, N., et al. (2016). Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells. Cancer Cell 29, 859–873.

Baba, M., Takeshige, K., Baba, N., and Ohsumi, Y. (1994). Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J. Cell Biol. 124, 903–913.

Takeshige, K., Baba, M., Tsuboi, S., Noda, T., and Ohsumi, Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J. Cell Biol. 119, 301–311.

Statins: From Cholesterol Control to Cancer Care

By: Joseph Longo

statinsFaced with increasing costs for the development of new drugs, researchers are now looking to repurpose older drugs as a relatively quick and inexpensive way of improving treatment options for cancer patients. One promising class of drugs that is receiving increased attention is the statin family of cholesterol-lowering medication. Statins have been used for decades to manage high cholesterol, and chances are that either you or someone you know is taking statins for this purpose. More recently, many studies have reported a link between statin use and reduced cancer risk and/or cancer-related death [1-4]. These observations have generated much excitement, as statins are already used in the clinic, are relatively cheap and are fairly safe, and therefore can be immediately repurposed to improve cancer patient care.

Repurposing statins to exploit a cancer cell addiction

Statins block a key pathway in cells that is important for the production of cholesterol and other lipid molecules. By blocking this pathway, statins lower the amount of these products inside the cell. In cancer, the products of this specific pathway are in high demand, as cancer cells rely on them for growth and survival. It is still unknown exactly how statins kill cancer cells, but many studies have shown that statin effectively “starve” cancer cells of these crucial products that are necessary for them to thrive [5]. Ongoing research is focused on identifying the specific products within this pathway that cancer cells are addicted to that make them sensitive to statin treatment.

Transitioning statins to the cancer clinic

Rarely are cancer drugs prescribed as a single therapy; rather, a combination of therapies is often prescribed to increase the effectiveness of the treatment and reduce the risk of relapse. Similarly, if statins are going to be repurposed to treat cancer, they will likely be co-prescribed with other treatments. Hence, an important focus of many current studies is to identify new and effective statin-drug combinations. For example, a recent phase II clinical trial evaluated the combination of high-dose pravastatin (a type of statin) and standard chemotherapy for the treatment of relapsed acute myeloid leukemia (AML). The authors of the study reported a 75% response rate, with 74% of the responders experiencing complete remission when given the statin drug alongside chemotherapy [6].

Despite evidence like this that supports the use of statins in the cancer clinic, other clinical trials have reported that statins offer no additional benefit when combined with standard therapy [7]. We need to better understand why some patients respond to this therapy while others do not, and use this information to better identify the patients who will benefit from treatment with statins. Moreover, if we can better understand why some patients do not respond, then we can identify more effective drug combinations that will work in these patients. Along this line, a recent study screened 100 clinically approved compounds and identified that dipyridamole, a drug approved for stroke prevention, increased statin-induced cell death in AML and multiple myeloma cell lines [8]. The statin-dipyridamole combination was also effective at delaying tumour growth in an animal model and killing primary AML cells collected from patients. Future clinical trials will be needed to assess the safety and effectiveness of this drug combination in actual cancer patients.

To date, over 100 clinical trials have tested or are actively testing if statins, either alone or in combination with other therapies, are effective at treating cancer. As the results of these studies become available in the coming years, they will inform us how best to use these clinically approved drugs in the fight against cancer. If the results are positive, then we will be in a strong position to immediately improve cancer patient care.

This article was written by Joseph Longo. Joseph is currently pursuing a PhD in the Department of Medical Biophysics at the University of Toronto. He studies how statins can be used to treat cancer. To learn more about Joseph and his research, check out our members page.

References

[1] Poynter et al. (2005). Statins and the risk of colorectal cancer. New England Journal of Medicine 352:2184-2192.

[2] Platz et al. (2006). Statin drugs and risk of advanced prostate cancer. Journal of the National Cancer Institute 98:1819-1825.

[3] Ahern et al. (2011). Statin prescriptions and breast cancer recurrence risk: a Danish nation-wide prospective cohort study. Journal of the National Cancer Institute 103:1461-1468.

[4] Nielsen et al. (2012). Statin use and reduced cancer-related mortality. New England Journal of Medicine 367:1792-1802.

[5] Mullen et al. (2016). Interplay between cell signalling and the mevalonate pathway in cancer. Nature Reviews Cancer 16:718-731.

[6] Advani et al. (2014). SWOG0919: a phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia. British Journal of Haematology 167:233-237.

[7] Kim et al. (2014). Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. European Journal of Cancer 50:2822-2830.

[8] Pandyra et al. (2014). Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Research 74:4772-4782.

Ready-or-not here we come: opening our eyes to the fight on cancer

By: Martin Smith, PhD

martin-open-eyes-blogCancer cells are locked into an epic game of hide-and-seek with our body.  Naturally, our body is tuned to recognize and eliminate foreign matter with the help of our immune system.  Cancer is no exception.  Routine inspection shows the presence of tumour infiltrating lymphocytes (TILs) deep inside of tumours removed during surgery.  These TILs are immune cells that have the natural ability to recognize and attack cancer cells in our body.  However, cancer cells can send out signals that shut down the ability of our immune system to recognize them.  In other words, they are effectively hiding from the immune system.  Recognizing this dangerous game of hide-and seek, scientists have learned how to isolate and expand the small number of TILs trapped in tumours in the lab so they can be reintroduced back into the patient.   The process of reintroducing the TILs into patients has become known as adoptive cell therapy (ACT) and shows promising results towards treating many types of cancer, such as metastatic melanoma, methothelioma, ovarian, breast and pancreatic cancers.

During surgery, complete removal of cancer with a rim of normal tissue around it called a clear margin. It is crucial for helping to prevent cancer from returning (1). Current efforts to assess whether the entire tumour has been removed rely on pre-operative imaging, post-operative reports, and the good judgment of physicians during the heat of surgery.  However, failure to fully remove the tumour can result in additional surgeries, delays in subsequent therapy, not to mention to the higher emotional distress of the patient and increases in health care costs. It is also possible that microscopic traces of tumour can remain to re-emerge at a later date.  A recent breakthrough comes from the lab of Réjean Lapointe at the Université de Montreal (2). He and his research team developed an “immuno-super gel” to help overcome some of the hurdles of current cancer therapies.   His 3D matrix gel, containing large numbers of cultivated TILs, may be poised and ready to destroy any cancer left behind during surgeries.  Imagine for a moment the potential for this technology.  The gel, charged with power of our own immune system, is injected into a surgical site.  Once there, the TILs multiply and migrate out of the gel into the surrounding tissue where they seek out and destroy the left over cancer cells not removed.   By destroying the left over cancer cells the new technology reduces the chances that any cancer will re-emerge.  This research has the potential to solve a pitfall in current cancer treatment by combining surgery with immunotherapy!

Scientists are continuing to push the boundaries of innovation by combining new technologies with ACT.  The technology behind the 3D gel matrix is a modified version of naturally occurring substances found in shellfish.  The chemical modifications provide additional matrix stability.  The leap forward comes from scientists discovering conditions that facilitate the physical support of the TILs, maintain them in a healthy state, and enable their slow release out of the gel.  Studies carried out in the lab have shown that these specialized immune cells released from the gel can kill cancer cells in a petri dish.  In a second part of the study, they also showed preliminary evidence that the gel is safe when injected into mice.  The safety and stability of a therapeutic is critical in the success of early-stage clinical trials.

If reading about exciting new therapies like this fosters a deep sense of hope and excitement; you are not alone.  The Canadian Cancer Society has recently released their top ten Canadian cancer discoveries of 2016 (3).  It’s no surprise that the immuno-super gel described here ranks among the discoveries which provide new insights into cancer biology and treamtment, turning the lights back on in the efforts to seek out ever last cancer cell in our body.

This article was written by Dr. Martin Smith. Dr. Smith completed his PhD at the University of Waterloo studying how proteins can cause cancer. He currently works for the Ontario Brain Institute where he studies brain disease. To learn more about Dr. Smith and his research check out our members page.

References:

1) Using 3D to fine-tune breast cancer surgery and save lives. Link:

http://www.cancer.ca/en/about-us/for-media/media-releases/ontario/2014/0929-using-3d/?region=on

2) Monette A, Ceccaldi C, Assaad E, Lerouge S, Lapointe R. Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies. Biomaterials. 2016 Jan (75): pp. 237-49.

3) Our top ten research stories of 2016, Canadian Cancer Society. Link: http://www.cancer.ca/en/about-us/our-research/research-impact/?region=on