Monthly Archives: January 2015

Latest Clinical Trials: Harnessing The Immune System To Fight Off Cancer With Immunotherapy

Immunotherapy PictureUnfortunately, the media often reports of cancer “breakthroughs” that are overhyped primarily because the conclusions are from studies done in mice or test tubes, and not human trials. However, for the past five years there were some genuine breakthroughs in cancer therapy (1). These breakthroughs are the result of using the power of the patient’s immune system to kill cancer cells – a theory that has been around for over a century. Our body is naturally equipped to remove abnormal cells, viruses as well as bacteria from our body. Clearly, this safeguard fails in patients that eventually get cancer; but in the last two decades, scientists have learned more about why some cancers can evade the immune system.

Research studies have shown that cancer cells can release molecules that block or kill the immune cells designed to kill the tumour. As a result of this research, drug companies went on to discover “Antibody Drugs” (such as, anti-PD-1 and anti-CTLA-4) that could prevent cancer cells from doing that. One of the biggest breakthroughs that used immunotherapy to fight cancer came in 2010 after a clinical trial for metastatic melanoma (the deadliest form of skin cancer) showed that the antibody-drug ipilimumab (anti-CTLA-4) quadrupled the number of surviving patients after 5 years (2). Unlike other cancer therapies, immunotherapy appears to have a long-lasting effect, which results in this long-term survival. The reason for this is that unlike chemotherapy, which kills cancer cells only during the course of the treatment, the immune system remembers how the cancer cells “looks like” compared to normal cells and it attacks any time the cancer tries to come back. The antibody-based therapy has been approved in US (in 2012) and Canada (in 2014) as first-line of treatment for malignant melanoma providing the first palpable success of immunotherapy. Many other successful human trials with these types of drugs in last few years spurred the development of a novel branch of cancer therapy: immunotherapy.

The antibody drug based immunotherapy holds great potential to fight cancer and other antibody-based drugs (checkpoint inhibitors) will be discovered with more preclinical research. Fortunately, in 2014 the Canadian federal government funded Biotherapeutics for Cancer Treatment (BioCanRx), which will investigate many aspects of immunotherapy. There will probably never be a single-drug cancer cure, but a combination of multiple therapies for an individual patient’s cancer. Immunotherapy will be one powerful weapon in this fight.

This article was written by Dan Cojocari. Dan is a PhD candidate in the Department of Medical Biophysics at the University Toronto. He studies how pancreatic cancer cells are able to survive in harsh tumor environments. To learn more about Dan and his research check out his bio on our members page.

References

  1. Scientists unleash the power of immunotherapy on stubborn cancers. The Globe and Mail, Jan 09, 2015.
  1. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Sep 23;363(13):1290.

Pembrolizumab (PD-1 antibody)

Ipilimumab (CTLA-4 antibody)

 

Dear 2015: I Commit To Butt Out

Sue Li Blog Article postLung cancer is the leading cause of cancer death in Canada and smoking accounts for more than 85% of these cases (1). While butting out is among the top 3 New Year’s resolutions, a surprising estimated 80% of people actually keep their resolutions for more than 24 hours (2). When it comes to smoking, it’s tough to quit cold-turkey. Did you know that it takes smokers an average of 7 attempts before actually being smoke-free?

Medications such as Nicoderm, Nicorette or the Varenicline (Champix) pill, act to substitute nicotine – the key addictive chemical in cigarettes – in our bodies. These drugs can help improve your chances of quitting, but the way in which your body handles nicotine may play a big role in determining which medication is the most effective for you. In a recent study, researchers compared quit rates among smokers on the nicotine patch to those given Champix and asked participants to state which was best to help butt out (3). It turns out the answer lies in the rate at which your body can break down (metabolize) nicotine. Researchers found that normal nicotine ‘metabolizers’ were more likely to stay smoke-free after 11 weeks of taking Champix than the nicotine patch. On the other hand, for slower nicotine ‘metabolizers’, the quit rates were similar regardless of whether they used the nicotine patch or took Champix. However, those treated with Champix reported more unwanted side effects, suggesting that this group of people would benefit more from using nicotine patches. While more studies will be needed, one thing is for sure – it’s never too late to quit!

P.S. Need an incentive to put a kick-start to quitting? Take the Canadian Cancer Society’s DrivenToQuit challenge. The rules are simple, quit smoking and win a car. The deadline to signup is Saturday February 28th, 2015. Click here for more details.

This article was written by Sue Li. Sue has a PhD from the University of Toronto and is currently working at Princess Margaret Hospital developing new drugs to treat prostate cancer. To find out more about Sue and her research check out her bio on the Members page.

References:

  1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014. Toronto, ON: Canadian Cancer Society; 2014.
  1. The Toronto Star: http://www.thestar.com/news/world/2013/01/01/new_years_resolutions_by_the_numbers.html. Accessed Jan 2015.
  1. Lerman C et al. (2014). Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomized, double-blind placebo-controlled trial. Lancet Respir Med. Jan 9 [Epub ahead of print].

Let’s Just Cross Our Fingers: Are We Powerless to Prevent Cancer?

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The answer seemed to be “yes”, earlier this year based on several news reports1,2,3 citing a cancer study published by Science4. The news claimed that two thirds of cancer cases are due to random bad luck. My immediate feeling was of relief; I thought that, since bad luck is the major player in cancer development, there is little sense in prevention. But on second thought, I wondered why cancer researchers would make such claims and how they reached those conclusions in the first place?

Next, I did something that I suspect not everyone does; I went to the primary source – the science article itself. Now I must admit, even as a cancer researcher this article took a lot of mental effort to understand, and I can see how the media may have gotten it wrong. Here’s a few questions I wanted to answer…

(1) WHAT WAS THE GOAL OF THIS RESEARCH?

This paper was written by two Johns Hopkins5 researchers who wanted to understand why cancers arise more frequently in certain body tissues (i.e. the colon) when compared to others (i.e. the brain).

(2) HOW DID THEY TRY TO ANSWER THEIR RESEARCH QUESTION?

In the study, they looked at 31 types of cancer (there are actually over 200 different types!) and compared the possibility – or risk – of getting those cancers to the number of times a stem cell divides within that same type of tissue. The researchers looked at stem cells because they are cells that (i) have long lives, (ii) renew themselves, and (iii) are responsible for generating and maintaining all the other cells in our tissues. Since they have a long life, they are more likely to accumulate detrimental changes in their genetic code, when compared to cells with a short life – those that make up the bulk of our organs.

(3) WHAT DID THEY FIND?

The researchers found that tissues whose stem cells divided more frequently were more likely to be sources of cancer, than tissues whose stem cells did not divide as often. In addition, the researchers found that the number of times stem cells divide largely explained differences in the risk of developing cancer, among the 31 types studied. In fact, the number of times stem cells divide could explain approximately two thirds of the possibility of getting cancer in one tissue versus another. Another important point of the study is that some tissues (i.e. the lung) have a high cancer risk, even though their stem cells do not divide very frequently. This shows that aside from number of cell divisions, both environmental (i.e. smoking) and inherited factors can play an important role.

(4) WHAT’S THE BIG PICTURE?

What this study actually tells us is that a significant proportion of cancers happen due to random genetic changes, but that lifestyle and hereditary factors DO play a role. These findings are in direct contrast with the reports in the media, which attributed bad luck as the cause of two thirds of cancers and suggested that we are powerless to prevent cancer. As you can see, it is essential to clarify what these findings mean for the general public, because “sensational headlines” have great power in influencing our behaviour. Although some cancers can occur at random, maintaining a healthy lifestyle and avoiding risky behaviours such as smoking or sun exposure, greatly impact our chances of preventing cancer. Finally, if even with prevention we are struck by “bad luck” and end up developing cancer, it is key to rely on early detection to target tumors that have not yet progressed to more aggressive stages.

This article was written by Natalia Ruiz. Natalia obtained a Master of Science degree from the University of Toronto studying the most aggressive and metastatic forms of breast cancer. To find out more about Natalia and her research check out her bio on the Members page.

References:

  1. CBC News: http://www.cbc.ca/news/health/two-thirds-of-cancers-caused-by-bad-luck-not-heredity-environment-1.2888125
  2. Yahoo News: http://news.yahoo.com/cancer-often-due-bad-luck-not-genes-environment-215201393.html
  3. BBC News: http://www.bbc.com/news/health-30641833
  4. Tomasetti C. and Vogelstein B. (2015) Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science, 347(6217):78-81