Stem Cells

29
Apr 2015
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Getting ready for Till & McCulloch Meetings 2015

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After last year’s conference in Ottawa, the Till & McCulloch Meetings are heading to Toronto.

The event — named in honor of Drs.

After last year’s conference in Ottawa, the Till & McCulloch Meetings are heading to Toronto.

The event — named in honor of Drs. James Till and Ernest McCulloch, who proved the existence of stem cells in the early 1960s — brings together Canada’s leading stem cell scientists, clinicians, bioengineers and ethicists, along with representatives from industry, government, health and non-governmental organizations from around the world.

This year’s agenda includes a special session with the Canadian Stem Cell Foundation, presented by James Price, Foundation President & CEO, and Dr. Alan Bernstein, Chair of the Board of Directors and President & CEO of the Canadian Institute for Advanced Research.

The Till & McCulloch Meetings, organized by the Centre for Commercialization of Regenerative Medicine, the Stem Cell Network and the Ontario Institute for Regenerative Medicine and sponsored in part by the Canadian Stem Cell Foundation, will take place at the Sheraton Centre Hotel in Toronto from October 26-28, 2015.

Registration is now open. Click here for more details.

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07
Apr 2015
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Dr. Molly Shoichet

Dr. Molly Shoichet and the future of regenerative medicine

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A few weeks ago, the University of Toronto’s Dr. Molly Shoichet was named as one of five recipients of the L’Oreal/UNESCO Women in Science Award.…

A few weeks ago, the University of Toronto’s Dr. Molly Shoichet was named as one of five recipients of the L’Oreal/UNESCO Women in Science Award.

Dr. Shoichet, the first Canadian to claim the prize since 2009, was recognized “for the development of new materials to regenerate damaged nerve tissue and for a new method that can deliver drugs directly to the spinal cord and brain.”

Dr. Shoichet, whose work is mainly focused on drug delivery and stem cell transplantation strategies, shares her excitement about stem cells and the field of regenerative medicine in a video interview with the Centre for Commercialization of Regenerative Medicine (CCRM).

“There is so much on the horizon of regenerative medicine that is exciting,” says Dr. Shoichet. “Our lab is really focused on the central nervous system, because there is really nothing apart from rehabilitation for these traumatic diseases like stroke, spinal cord injury and even blindness.”

You can view the other installments in the Regenerative Medicine Leadership Series here.

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31
Mar 2015
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Liver failure: the promise of stem cells

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As March makes its exit — like a lion in some regions, like a lamb in others — it’s good to remember that it marked “Liver Health Month,”an initiative to raise awareness of liver diseases.…

As March makes its exit — like a lion in some regions, like a lamb in others — it’s good to remember that it marked “Liver Health Month,”an initiative to raise awareness of liver diseases. Each year the  Canadian Liver Foundation, a national not-for-profit organization established in 1969 to support liver research and education, devotes this month to spreading information about liver health to Canadians.

Liver is the largest solid organ and the biggest reservoir of blood in the body, critical for maintaining overall health. It metabolizes nutrients, removes waste products, filters toxic substances and drugs, maintains the levels of blood sugar, fat and hormones and participates in immune responses.

Hepatocytes are the predominant cell type in the liver and they perform most of its functions. However, their short lifespan requires the liver to constantly regenerate itself in order to remain healthy.

It is estimated that one in 10 Canadians, or around 3 million people, have some form of liver disease. There are over 100 different kinds of liver diseases and the most common forms are viral hepatitis, fatty liver disease and liver cancer. Causes range from alcohol consumption, viruses, obesity, genetics, autoimmune diseases, drugs, toxins.

Liver disease can be difficult to diagnose because the symptoms can be vague or non-existent until the disease has advanced. Although the liver can continue to function despite a great deal of abuse, once it reaches a state of failure the damage is irreversible.

Currently, the only available treatment is transplantation, but the demand for organs is so high that many people with liver failure die before receiving a donation. While there is no stem cell treatment for liver failure as of yet, stem cells could one day represent a reliable option. Many research teams around the globe are working on developing effective stem cell therapies for liver failure.

In 2013, researchers from Yokohama City University in Japan demonstrated they could produce liver buds, or miniature precursors to human livers, by using stem cells taken from bone marrow, blood vessels and skin cells. When the researchers implanted the buds into the brains of mice, they observed that they connected with the mouse’s blood system. After a couple of months the buds looked and acted like liver and produced liver-specific proteins.

The scientists believe the research is promising, but challenging and it will take to translate this work into a way of growing new livers for patients.

“Testing whether liver buds could help sick patients is years away,” said Professor Takanori Takebe, who led the researchin Nature. “Apart from the need for longer-term experiments in animals, it is not yet possible to make liver buds in quantities sufficient for human transplantation.”

In the meantime, you can find more information about stem cells and liver failure in our Toward Treatments section. Click here to read more.

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27
Feb 2015
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What is Denis-Claude Roy excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Denis-Claude Roy, Director of the Centre de recherche de l’Hôpital Maisonneuve-Rosemont and a full professor at the Université de Montréal. Dr. Roy is Chief Executive Officer of CellCAN Regenerative Medicine and Cell Therapy Network. Asked about what he sees developing in the field of stem cells and regenerative medicine he provided the following highlights of his work and others.

In our work with blood-based cancers like leukemia and lymphoma, we have developed a protocol for stem cell transplantation for people who don’t have a matched donor. We are able to do mismatched stem cell transplants, or what’s called haploidentical stem cell transplantation. This means that in place of being fully compatible (with the donor cells), a patient can be 50% compatible and still get a transplant.

Normally (such a transplant) would kill the patient, but we’ve developed a strategy to eliminate the cells that cause Graft Versus Host Disease (GVHD) and attack the patient. GVHD is probably the biggest problem associated with stem cell transplantation. Instead of having the patient develop GVHD or treating the patient with drugs to prevent it from occurring, we treat the cells in the lab and eliminate those that cause GVHD. So, we’re able to do stem cell transplants without immune suppression and the patient won’t have to take immuno-suppressor drugs for the rest of their lives.

We’re very excited about this. Our first study included 19 patients and we have had extremely good results. The patients had few infections and low relapse rates. A second study on another 23 patients, part of an international study, is currently led by our centre. To date, patients are again doing very well.

We’re also starting a clinical trial using a molecule called UM171 that was developed by Dr. Guy Sauvageau (Université de Montréal) to expand umbilical cord blood stem cells while maintaining their properties. Right now, donated umbilical cords have too few cells to treat adults. One donation provides enough cells to treat a child, but not enough for a normal size adult. Currently for an adult, we have to use two donations and that presents immune issues and is very expensive. We want to ramp up the number of stem cells from umbilical cord donations for those patients that have a match but not enough cells. We can grow the cells in the lab to have enough for the transplant.

This will allow us to select from our larger pool of umbilical cord blood donations and therefore improve the match, which should result in decreasing the number of complications associated with transplants and make it possible for more people to get them. This could also accelerate engraftment, shortening the time for the cells to engraft, which would decrease risk associated with the procedure.

The the use of stem cells in cardiac treatments is also starting to gather momentum. Dr. Duncan Stewart (University of Ottawa) has a trial (using genetically modified stems to repair heart damage) that is going very well. I am also working with Dr. Nicolas Noiseux (Université de Montréal) on activating stem cells before they are infused into the heart. He is studying a number of molecules to activate the cells before they are injected. The idea is to repair the hearts of patients who have poor cardiac function.

We will also be starting a trial using cells from the immune system to target leukemia. They are specific, acting like missiles, which will select and kill leukemia cells. Dr Claude Perreault (Université de Montréal) is developing a series of new targets. A new clinical trial is likely to start in the Fall.

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25
Feb 2015
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What is Connie Eaves excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Connie J. Eaves is a Distinguished Scientist at Vancouver’s Terry Fox Laboratory, which she co-founded. A Professor of Medical Genetics at the University of British Columbia, she is world-renowned for her pioneering research in basic blood stem cell biology, which led to new treatments for leukemia. She also isolated breast stem cells and is a leading thinker in the field of breast cancer. Here’s what she’s excited about in 2015.

I was a co-author of a Nature paper in December that was led by Drs. Samuel Aparcio and Sohrab Shah (University of British Columbia) and described the changing genomic composition of breast cancer xenografts — that is fragments of patients’ breast tumours growing in special transplanted mice that have no immune system.  In such mice, many patients’ tumours can grow as if they were still in the patient. You can thus track how the tumour evolves in relation to the original tumour.

This model has significant implications for developing new ways to treat cancer, because you can use the tumours created in the mice to determine which treatments work best and how that compares to the mutations that were present in cells that disappeared and those that may be unique to the cells that proved resistant. Groups all over the world are trying to use this approach, so we’re excited about that.

My lab has another paper in the works that has to do with making human breast tumours starting with normal human breast tissue. We have developed a protocol in which normally discarded breast tissue samples obtained from women undergoing cosmetic surgery are infected with a mutant cancer-causing gene and then produce tumours when transplanted into immunodeficient mice.

The reason this is extraordinarily exciting is because people have been trying to do this this for years with blood cells and it’s been difficult: you can count on one hand the number of different mutant genes (out of many tried) that can produce a leukemia when put into normal human blood-forming cells.  Indeed, this has been very discouraging in the leukemia field.

The idea is, if you could study the early events that cause leukemia or breast cancer, then you would be able to look into the first changes that occur and get a handle on those. You could then look for those changes in a patient’s samples and try to target them specifically.  Since they are the first events, they are likely going to be in every daughter tumour cell in that patient and hence better (more universal) targets.

One of the problems with treating many tumours is their genetic instability, which leads to the genesis of a tremendous diversity of subclones of cells carrying additional new mutations. Thus when you use a treatment strategy that can kill a dominant clone, there may be another 100 subclones that are not eliminated lurking at lower levels that then regrow.  That is why the idea of understanding how a tumour starts to develop from its earliest stages is so captivating.  Being able to do this with human breast tissue was unexpected and opens the door to all sorts of experiments. So we’re very excited about this new line of work.

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24
Feb 2015
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Cystic Fibrosis: the promise of stem cells

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Cystic fibrosis (CF) is the most common fatal genetic disease affecting Canadian children and young adults. One in every 3,600 children born in Canada has CF, which occurs when a child inherits two abnormal genes, one from each parent.…

Cystic fibrosis (CF) is the most common fatal genetic disease affecting Canadian children and young adults. One in every 3,600 children born in Canada has CF, which occurs when a child inherits two abnormal genes, one from each parent. Approximately, one in 25 Canadians carry an abnormal version of the gene responsible for CF. Carriers do not have CF, nor do they exhibit any of the symptoms of the disease.

Over 4,000 Canadians live with CF, which affects their lungs and digestive system, where the linings of these vital organs become clogged with thick mucus. This can lead to chest infections, persistent cough, wheezing and shortness of breath, bowel disturbances, weight loss or failure to gain weight, salty tasting sweat, infertility in men and decreased fertility in women.

The median age of survival for Canadians with CF was 50.9 years in 2013, over 25 years higher than it was in the early 1980s. However, the complications of ongoing infections and inflammation in the lungs, which eventually lead to loss of lung function, cause death in the majority of people with CF. Other frequent complications include difficulty in digesting fats and proteins and vitamin deficiencies due to loss of pancreatic enzymes.

While there is no cure for CF, remarkable progress in CF research has been made since 1989, when Canadian researchers at the Hospital for Sick Children (SickKids) discovered the gene responsible for CF — CFTR.

“Over the past decade there has been tremendous progress with regard to therapy discovery conducted using generic cells induced to possess a particular CF mutant protein,” Dr. Christine Bear, Senior Scientist and Co-Director of the CF Centre at SickKids, said in a press release. “While this approach led to the discovery of a drug called Kalydeco, we believe that a new discovery strategy is needed during the upcoming 10 years to find the next generation of therapies effective in treating all CF patients.”

Dr. Christine Bear

Dr. Christine Bear

Kalydeco is also a very expensive medication, one that is not covered by all provinces in Canada. Also, because of different CFTR mutations and the uniqueness of each patient, Kalydeco is only effective for a small population of those with CF.  “While this is a big step for CF, there is still much work to be done,” added Dr Bear.

Stem cells may provide some of the answers Dr. Bear and others are searching for. Cystic Fibrosis Canada, a national charitable not-for-profit corporation established in 1960 to find a cure or control for CF, recently funded Dr. Bear and her team at SickKids for their project, ‘Individualizing cystic fibrosis therapy.’

Dr. Bear’s lab is developing a resource of induced pluripotent stem cells or iPS cells from a cohort of patients with CF to represent the Canadian patient population. Patient-specific iPS cells will then be differentiated into lung epithelium and used to assess, explain and eventually predict individual specific responses to emerging therapies.

The approach, the first of its kind in Canada, will enable the future implementation of techniques to monitor functional correction of CFTR — techniques that are essential for pre-clinical trials comparing patient-specific responses to CF therapies and the identification of the best treatment for each CF patient.

While the work is in the early stages, it does offer hope that new approaches defeating CF can be made available some day soon.

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20
Feb 2015
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janet rossant rock star video3

What’s Janet Rossant excited about?

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Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.

Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s premier instalment, we interviewed Dr. Janet Rossant, Chief of Research and a Senior Scientist at The Hospital for Sick Children in Toronto and immediate past president of the International Society for Stem Cell Research. She provided the following highlights.

When I look broadly, I’m seeing a lot of excitement about being able to use stem cells to model human disease. Here in Toronto, we’ve made induced pluripotent stem (iPS) cells from patients with cystic fibrosis, cardiac diseases and autism. We’re beginning to use those cells to differentiate them into different cell types to study the diseases in a Petri dish.  All of that is moving forward. We’re going to see more and more of that.

I think, though, that the area to watch is a little bit more than just taking iPS cells and growing them in a Petri dish in a flat culture but instead growing cells and making little organs or “organoids.” We’ve seen over the last year people making little organoids in a dish: gut organoids, stomach organoids. I’m expecting to see papers on lung organoids.  This means we will be able to study diseases in new ways and use these organoids for doing drug screening.

We’re also seeing the first trials (by Viacyte, a California-based cell-therapy company) going forward with pancreatic progenitor cells for treating type 1 diabetes. We probably won’t get full results, because these are all Phase 1 trials, but we’re going to get some idea of the survival and effectiveness in a relatively short period of time.  Canada will be one of the sites for that trial; Dr. James Shapiro (University of Alberta) is involved.

There have been good Canadian contributions to that. The Viacyte trial is done with pancreatic progenitors that will mature and make the right insulin producing cells. Other people feel you’d be better off starting with the insulin-producing cells and using those directly.  A recent paper from Dr. Tim Kieffer (University of British Columbia) shows really good advances in generating functional beta cells. It gives you a lot of hope that this kind of trial, which is an early one, will be rapidly replaced by better trials and better cells. Dr. Cristina Nostro (University of Toronto) is also moving very fast at getting better and better pancreatic islet cells.

The technology that everybody is jumping on is genome editing.  Now you can think not only about fixing people with stem cells, but you can think about fixing the genetic defects in people’s stem cells before you put them back. Certainly here at SickKids there are a number of people thinking in the very short-term mode about how they might translate that into gene therapy approaches to genetic diseases.

The expanded use of cell-based therapies — whether they are stem cells or other cells — is also having an impact. If we think about immunotherapy for cancer, we’re using either molecules or modified T-cells.  We’re seeing cell-based therapies of all sorts coming forward.

We’re seeing expanded use of bone marrow transplantation for a wider range of autoimmune diseases.The trials that Dr. Harry Atkins (University of Ottawa) and others are doing on MS — those kinds of approaches are going to get more and more refined as we go forward.

Cardiac care is another area where we’re seeing clinical trials with many kinds of cells and molecules to treat heart disease. I think we’re going to see small incremental advances. A big advance has to come if we can actually fix the heart muscle.  I know Dr. Gordon Keller (University of Toronto) and his colleagues are pushing very hard in that direction to try to move from cells in culture to bioengineered matrices of cells that you could think about using to replace damaged parts of the heart.  Also, Dr. Michael Fehlings (University of Toronto) is very active in looking at a number of sources of cells that might be able to remyelenate axons in spinal cord repair.

These are all areas to watch in the future — the whole field is moving rapidly forward.

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12
Jan 2015
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Diabetes trial cleared by Health Canada

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Recently, we blogged about the first U.S. patient successfully implanted with a device to treat type 1 diabetes.

Good news is that the VC-01 device will soon be tested on Canadian patients.…

Recently, we blogged about the first U.S. patient successfully implanted with a device to treat type 1 diabetes.

Good news is that the VC-01 device will soon be tested on Canadian patients. After the U.S. Food and Drug Administration approval of the testing in August 2014, Health Canada has now cleared the beginning of the Phase 1/2 clinical trial of the VC-01 in Canada.

The device, developed by the American company ViaCyte, is about about half the size of a credit card and can be implanted under the skin from where its progenitor cells secrete insulin whenever blood sugar levels get too high, restoring glycemic harmony. It is being tested at the University of California, San Diego Health System for its safety, tolerability and efficacy in patients with type 1 diabetes who have minimal to no insulin-producing beta cell function.

“The first cohort of patients in this two-cohort dose escalation study of the VC-01 product candidate is currently being assessed at a single site in the United States. Health Canada’s approval represents further validation of the trial and allows us to expand internationally to one or more sites in Canada.” Dr. Paul Laikind, President and CEO of ViaCyte said in the press release.

The location and enrollment start date of the Canadian trial site are yet to be released, but there is already a strong connection between Canada and ViaCyte. Edmonton’s Dr. James Shapiro, Director of the Clinical Islet Transplant Program at the University of Alberta, is a scientific advisor with ViaCyte. In 1990s, Dr. Shapiro co-developed the Edmonton Protocol, a procedure for implementing pancreatic islets for the treatment of type 1 diabetes.

Although the VC-01 clinical trial is in its early stages and it is unsure whether it will become a safe and efficient treatment option for diabetes, it represents an important step towards a cure for the disease.

Learn here how up to 10 treatments for chronic diseases will be developed over the next 10 years thanks to the Canadian Stem Cell Strategy & Action Plan.

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08
Jan 2015
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Could we fight obesity with a pill?

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As the new year rolls out and people struggle to keep their resolutions to shed excess pounds, it’s good to know stem cell scientists are on the case.…

As the new year rolls out and people struggle to keep their resolutions to shed excess pounds, it’s good to know stem cell scientists are on the case.

In December, researchers from Harvard Stem Cell Institute (HSCI) showed they are one step closer to creating a pill that could help control obesity.

Obesity occurs when there is an accumulation of body fat in the form of white fat cells. In most cases, it is caused by an excessive intake of calories and inadequate exercise to burn them off. About 6 million Canadians are living with obesity, which can lead to Type 2 diabetes, high blood pressure, heart disease, stroke and many other severe health conditions.

As described in the report published by Nature Cell Biology, the HSCI team identified two compounds that can turn “bad” white fat cells into “good” brown fat cells. Brown fat cells  burn excess calories and reduce the number of white fat cells in order to generate heat.

While the discovery of the compounds is promising, there could be side effects on the immune system. Dr. Chad Cowan of Harvard’s Department of Stem Cell and Regenerative Biology, warned that “if you administered the compounds for a long time, the person taking them could become immune-compromised.” That would make them more prone to infections.

In addition, as Dr. Cowan explained in CTV’s report, “the pill will never replace a healthy lifestyle, but can definitely benefit the patient population at risk.” The pill, in fact, would not be able to bring the benefits of physical exercise.

The transition from this discovery to a safe clinical treatment will likely take many years. However, “a decade of hard, basic science work is paying off,” said to Dr. Cowan,  “The good news/bad news is that science is slow. We thought that working with stem cells would lead to the discovery of new drugs and therapies, and now it’s really starting to happen.”

Discover how the Canadian Stem Cell Strategy & Action Plan will accelerate the development of stem cell treatments for several diseases over the next decade. Click here to find out more.

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06
Jan 2015
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Researchers find many cancers are ‘bad luck’

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Credit: C. Tomasetti, B. Vogelstein and illustrator Elizabeth Cook, Johns Hopkins

We all know that unhealthy lifestyles and genetics increase the risk of developing cancer, but a new study suggests that hereditary or environmental factors are not the primary cause of two-thirds of cancer types.…

Credit: C. Tomasetti, B. Vogelstein and illustrator Elizabeth Cook, Johns Hopkins

Credit: C. Tomasetti, B. Vogelstein and illustrator Elizabeth Cook, Johns Hopkins

We all know that unhealthy lifestyles and genetics increase the risk of developing cancer, but a new study suggests that hereditary or environmental factors are not the primary cause of two-thirds of cancer types. Instead, misfortune plays a large part.

According to the study, published in Science and widely reported on in the media, 65% of adult cancers are mainly due to “bad luck,” or random genetic mistakes that occur during the process of cell division in the body.

“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” DrBert Vogelstein of the Johns Hopkins University School of Medicine said in a media release.

Cell division is constantly happening in the body to replace old cells. Sometimes genetic mutations occur during the process. As might be expected, the risk of mistakes increases with the increased number of cell divisions. Drs Vogelstein and Cristian Tomasetti, analyzed the total number of stem cell divisions in 31 tissue types during an individual’s lifetime, excluding breast and prostate cancers. They estimated that 22 cancer types were a result of genetic mutations occurring during the normal cell division process and could not be avoided. These include leukemia, pancreatic, bone, ovarian and brain cancers.

“If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then we should focus more resources on finding ways to detect such cancers at early, curable stages.” said Dr. Tomasetti in a report by The Telegraph carried in the National Post.

According to the researchers, other cancers, such as colorectal, skin and lung cancers are heavily influenced by genes and exposure to cancerous agents, such as smoking for lung cancer, UV exposure for skin cancer and poor diet for colorectal cancer.

Does the new finding mean we should abandon our efforts to prevent cancer? Not at all.

“Everything we know about altering lifestyles to prevent cancer from the environmental point of view we absolutely need to continue doing. If anything our finding puts more stress on the need to spend even more money on early detection,”  Dr. Tomasetti told Time magazine.

“About half of all cancers can be prevented through healthy living and healthy public policies,” Gillian Bromfield of the Canadian Cancer Society said in a statement. “We encourage Canadians to lower their risk of cancer by not smoking, eating well, being active, sitting less, maintaining a healthy body weight, limiting alcohol, being safe in the sun and avoiding indoor tanning.”

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