Coley’s toxins and the birth of cancer immunotherapy

[from the cutting-room floor…] (Image source: Wikipedia)

Elizabeth Dashiell walked into the Memorial Hospital in New York with what she thought was probably a minor – albeit annoying – complaint. A small, painful nodule had formed on the back of her hand after she had jammed it between two seats on a train a couple of months earlier. Her doctor, a young surgeon by the name of William Coley, was perplexed. The lump had all the signs of an infection, but investigations finally led Coley to conclude that Bessie had sarcoma, a type of cancer.

The year was 1890 – a time when cancer was an almost guaranteed death sentence. On November 8, just five weeks after he had first seen his 17-year-old patient, Coley amputated Bessie’s right hand and forearm in an attempt to save her life. But even amputation proved futile, and Bessie died two and a half months later, riddled with tumours that had sprouted throughout her body.

Coley, just 28 at the time, was devastated by his patient’s rapid demise and resolved to find a way of preventing similar deaths in the future. Trawling through hospital medical records for clues to a possible cure, he stumbled upon the case of a German immigrant named Stein. Surgeons had repeatedly attempted to remove Stein’s neck cancer without success – the tumour stubbornly regrew each time. Until, that is, Stein succumbed to a severe post-operative skin infection. On this occasion, his tumour had shrunk and disappeared, leaving Stein cancer-free.

Coley suspected he had discovered something important and began deliberately injecting his patients’ tumours with bacteria – first live, and then killed – hoping to replicate Stein’s mysterious cure. Over the ensuing years, Coley tinkered with his formulation to find just the right combination of bacterial strains to produce a robust fever and tumour remission. He went on to treat hundreds of people with his ‘Coley’s toxins’, effectively curing a quarter of his sarcoma patients – a remarkable achievement for the time.

“Even though his work started over 100 years ago, he was really quite advanced [for his time],” says Stephen Hoption Cann, an immunologist from the University of British Columbia in Canada and chief medical officer at MBVax Bioscience, a small biotech firm in Vancouver.

Coley had figured out how to harness the body’s natural defence system to combat cancer. After his death in 1936, Coley’s toxins fell out of use. Patients required multiple doses, often of increasing strength, so “treating patients was a little more involved,” says Hoption Cann. With Coley no longer available to provide advice on how best to modify the dosage for each patient, and other simpler therapies, like chemotherapy and radiation therapy gaining favour, the idea of utilising the immune system to treat cancer was largely forgotten.

Coley’s work has belatedly earned him a distinguished place in medical history. Many now regard him as the father of cancer immunology, a field that has attracted increasing attention over recent years and was last year singled out as the ‘Breakthrough of the Year’ by the prestigious journal Science. Hoption Cann and others have been picking up where Coley left off, investigating treatments that kick-start the immune system to fight cancer.

To read more about current cancer immunotherapies, check out my feature in Cosmos Magazine, Is immunotherapy a cancer game changer? [paywall]

 

Game Changer for Cancer

From Cosmos Magazine, June 13, 2016. (Image: Melanoma by Martin Trotter via Flickr)

RON WALKER has never been one to shy from a challenge. But at 72, the former lord mayor of Melbourne was thrown a curveball. A pea-sized lump on his forehead turned out to be a melanoma.

Once removed, and with the lymph nodes showing all clear, his surgeon was optimistic. Within a year tumours blossomed in his lungs, bones and brain. Walker was given a few months to live. In a last-ditch attempt, he travelled to Los Angeles to enrol in a trial of a new drug, Keytruda. Every three weeks, Walker watched drug-laced fluid drain from the drip into his arm. After just four treatments, his tumours began shrinking. A year and a half later, his cancer was nowhere to be seen. Similar stories of survival against the odds are found across the globe, given prominence by celebrity recipients such as former US President Jimmy Carter, who used the drug to great effect in his fight against melanoma.

Keytruda and similar drugs are heralded as game-changers in the cancer community.

Read more…

Breast cancer: to screen or not to screen?

Piece of cake? (Credit: The Mayor of Worldwide Breast Cancer)
Piece of cake? (Credit: The Mayor of Worldwide Breast Cancer)

Last month, the results from 25 years follow-up of a Canadian trial into mammographic screening for breast cancer were published. The conclusion: breast cancer screening could be doing more harm than good.

The study found no benefit, in terms of reduced mortality, in women who were screened. More concerning, though, was the conclusion that one in five women who were treated for breast cancer in the screened group were unnecessarily treated — they potentially had lumps or entire breasts removed, were subjected to radiation therapy, hormone therapy, or chemotherapy, when their cancers would not have posed them any threat in their lifetime. In other words, they were over-diagnosed.

The line between benefit and harm when it comes to breast screening seems to be getting ever finer. Other studies have also pointed to significant rates of over-diagnosis in breast screening, yet advocates — and many women who have had lumps detected by mammography — maintain that screening is beneficial.

I recently wrote a piece for ABC Health & Wellbeing that tries to pick through the data. For many, the bottom line is that whatever the evidence, women should be given all the information available about benefits as well as potential risks, especially given that they are being invited to participate voluntarily. Check it out here.

 

Inherited risk: The benefit and burden of genetic testing for heritable diseases

Not too long ago, if you wanted to know whether you were at risk of breast cancer or Alzheimer’s disease, you looked at your family tree. Did a parent, an aunt or an uncle succumb to the disease? Do any of your siblings have the condition? But for an increasing number of life-threatening diseases, genetic tests that can help predict whether you’re at risk now exist.

The cost and time needed to sequence a single gene, or even an entire genome, has plummeted over the last two decades. And it’s not only doctors wanting to diagnose an illness who are taking advantage of the genomic riches now so readily available. Today, people can send their own blood or saliva samples to a growing number of direct-to-consumer genetic testing companies. The future of this trend is uncertain, though, as it has attracted the scrutiny of both the research community and government regulators.

But when it comes to genetic testing, knowledge isn’t always power. Divining your medical future based on the code in your chromosomes can have far-reaching consequences for yourself and for those around you.

On the latest episode of Up Close, I discuss how clinicians, patients and their families navigate the often uncertain waters of genetic testing with clinical and research geneticist Professor Ingrid Winship. Professor Winship is the Executive Director of Research at Melbourne Health and Professor of Adult Clinical Genetics at The University of Melbourne and the Royal Melbourne Hospital.

 

The antioxidant paradox: supplements could be doing you more harm than good

Medical Drugs for Pharmacy Health Shop of Medicine
Don’t swallow that pill: antioxidant supplements can be more harm than good (Photo credit: epSos.de)

Supermarkets are full of products that market themselves as superfoods and spruik their antioxidant content, but are antioxidants as healthy as we’ve been led to believe?

Ever since large observational studies linked antioxidant-rich diets with good health, taking antioxidant supplements has seemed like a healthy way of boosting our antioxidant intake. But rigorous ransomised controlled trials of antioxidant supplementation gives us pause for thought. It turns out that antioxidant supplements don’t fight the ravaging effects of free radicals in our body. In fact, supplements containing beta-carotene and vitamin E can actually worsen our health prognosis and decrease the benefit we get from clearly healthy activities like exercise.

One of the clearest illustrations of the negative effects of antioxidant supplementation comes from a Finnish study that looked at beta-carotene supplementation in smokers. Over 29,000 men were followed for five to eight years, and those given beta-carotene were more likely to develop lung cancer than those on the placebo.

Last week, I wrote an article for ABC Health and Wellbeing, explaining what antioxidants and free radicals are, and what the evidence is on their health effects. Check it out here.

Cycling to chemo: exercise during cancer treatment

Forget the anti-oxidant–rich red wine and chocolate. If you really want something that’s going to prevent cancer, start exercising. Not only does exercise help to prevent a raft of life-threatening conditions such obesity, type 2 diabetes and high blood pressure, and play a role in keeping mental health in check by preventing depression and anxiety, but it can also be both a preventive and remedial factor in cancer.

Exercise can reduce the risk of developing a range of cancers including colon cancer, prostate, lung and gastrointestinal cancer in men, and breast and endometrial cancer in women. It can also improve long-term prognosis for cancer survivors.

There is now also emerging evidence that maintaining or commencing exercise as soon as you are diagnosed can be beneficial. This means that the common advice to take it easy and relax is actually completely wrong. Even while undergoing chemotherapy and radiotherapy, people should do as much exercise as they can to reduce symptoms like fatigue and improve physical fitness and functioning.

A few days ago, ABC Health & Wellbeing published a piece I wrote for them about exercise during cancer treatment. Check it out here.

Aspirin keeps stomach cancer at bay

Aspirin
Aspirin (Photo credit: tomazstolfa)

Taking aspirin a few times each week, or regularly for years decreases the risk of stomach cancer.

The ancient Greeks were well aware of the power of willow bark powder to relieve headaches, pain and fever. But not even Hippocrates, widely considered the father of Western medicine and whose records speak of the use of willow bark in ancient times, would have been aware of aspirin’s cancer-fighting properties.

In recent years, aspirin and other non-steroidal anti-inflammatory drugs have been shown to reduce death rate from multiple types of cancer by around 20 per cent. Studies have found that aspirin decreases the risk of developing cancers of the breast, skin, colon and oesophagus – the muscular tube that delivers food from the mouth into the stomach. Continue reading “Aspirin keeps stomach cancer at bay”