Please note, Cancer Revolution: Science, innovation and hope ended at the Science and Industry Museum in Manchester on 27 March 2022, and will be at the Science Museum in London from 25 May 2022 – January 2023.
This blog post was written with Deborah James in August 2021, and updated in May 2022.
Earlier this year the Science Museum Group awarded a fellowship to cancer campaigner Deborah James, an award that has gone to many distinguished individuals ranging from Sir David Attenborough to Dame Sarah Gilbert.
The fellowship was awarded at a special dinner at the Science Museum attended by Deborah and her husband Sebastien, ‘in recognition of her tireless work on social media, along with blogs and articles, which has spread positivity and awareness about cancer research, treatments and the experience of patients, and has highlighted the importance of early diagnosis and research to a wider audience.’
Deborah provided invaluable support to the Science Museum Group, especially in relation to the Cancer Revolution exhibition. Developed by the Science Museum Group, with the support of expert partner Cancer Research UK, it welcomed tens of thousands of visitors at the Science and Industry Museum, Manchester and will open at the Science Museum in London from 25 May.
When I talked to her about her treatment last year she was hoping to see her 40th birthday in October 2021, outliving her wildest expectations given she was diagnosed with incurable cancer around five years ago: ‘I am really looking forward to the launch of the exhibition.’
She celebrated her 40th but, in May of 2022, her health took a turn for the worse.
A member of the advisory board for the exhibition, which I chair, Deborah has played an extraordinary role in bridging the gap between cancer research, the clinic, and the public.
Her encounter with cancer dates back to 2016. Deborah was fatigued, losing weight, and passing blood. After being repeatedly assured by her GP that tests suggested all was well, she signed up for private colonoscopy.
She later wrote about the moment, just before that Christmas, when she was first confronted with her cancer: ‘Having refused the sedative and having researched what cancerous tumours would appear like in a colonoscopy (total hypochondriac geek alert!), I stared my ugly 5.5cm cancerous, ulcerated Stage 3 tumour in the face and everything went silent.’
According to Cancer Research UK, there are more than 42,000 cases diagnosed each year, making it the fourth most common cancer. There are common risk factors, but Deborah was then a 35-year-old vegetarian who was fit, being a former national gymnast. The mother to two young children and deputy headteacher did not fit the profile of those likeliest to develop the disease.
She began to blog, as BowelBabe, reporting how her tumour was removed in January 2017 and she began chemotherapy to destroy any remaining cancer cells. By then, the seriousness of her cancer had been revised upwards.
In fact, Deborah had a Stage 4 tumour—scans revealed that disease had already spread to other organs, her lungs. (To remove the tumours from her lungs would take another six operations.)
In April 2017 she was told that she had a mutation in her tumour’s DNA that disrupted the BRAF gene, which is normally involved in a pathway of signals that tell healthy cells when to grow and divide, suppressing ‘programmed’ cell death, known as apoptosis.
But in her tumour the gene was active all the time, causing the abnormal growth that is the mark of all cancer. When Deborah Googled what this meant, she found her prospects were bleak. As she blogged, the BRAF cancer is ’only the rarest and hardest to treat due to its unresponsiveness to chemo, aggressive make up or lack of ‘wonder’ immunotherapy cure. Brilliant!’
She appeared on BBC Breakfast and, ever since, has candidly documented her struggles with the disease in a column for the Sun newspaper and as presenter of the BBC podcast You, Me and the Big C, conceived by her co-host Rachael Bland, who died of breast cancer in September 2018.
Hope, grit, science, and disease collide in Deborah’s story where she has drawn on the latest techniques, from experimental drugs to cutting edge ’focal therapies’. The latter, used by her Royal Marsden Hospital interventional radiologist Nicos Fotiadis, include going under a CyberKnife, which delivers targeted form radiotherapy to attack an inoperable lymph node, and the use of needle-like probes that can destroy small tumours with heating and freezing, or even a NanoKnife, which punches holes into cancer cells with low energy electrical pulses.
I did it! Concurrent Cyberknife and Radiotheraphy course done! Knackered and elated! Thankyou to the real life angels that carried me up and over the wall I hit a few days ago. #Cancer in the time of #COVID19 – a head screw right there! Thank you @royalmarsden #nhs @NHS pic.twitter.com/sLZ4zXSwHm
— Deborah James (@bowelbabe) May 15, 2020
Hoping another tumour blasted! BIG ❤️ to the Interventional radiology team at the @royalmarsden who as always have been amazing. 8th time with them! Now it’s nanoknife! Apparently all I talked about was going on holiday as I came round! Can’t recall a thing! #covid #dreaming pic.twitter.com/rBv04EoMPu
— Deborah James (@bowelbabe) April 26, 2021
As our Cancer Revolution exhibition shows, the challenge with cancer is that, as our immune system fights the renegade cells, and oncologists treat them with cancer drugs and radiation, new mutations take hold so that the cancer constantly evolves to outwit our defences or treatments, developing resistance.
The value of adopting this Darwinian view was spelt out by fellow exhibition advisor, Prof Charlie Swanton, co-director of the CRUK/UCL Lung Cancer Centre of Excellence, Group Leader at the Francis Crick Institute and Cancer Research UK’s Chief Clinician:
‘We and others are finding evidence for the enormous genetic diversity in cancers at the single cell level, when they can be composed of billions or even trillions of cells.
‘The genetic diversity between cells in the same cancer in an individual patient provides the fuel upon which natural selection acts, allowing cancer cell resistance to drug therapies to emerge, leading to treatment failure. Finding new approaches to target cancer evolution and limit adaptation and drug resistance, is the focus of many cancer laboratories across the planet.’
One way to limit the ability of a tumour to evolve resistance is to use a handful of drugs that target different cancer growth pathways at the same time. Deborah was inspired at a Cancer Research UK event by research on this approach presented by Prof René Bernards and colleagues at the Netherlands Cancer Institute. Bowel cancer cells are insensitive to drugs that inhibit BRAF—they harness other pathways to grow—and Prof Bernards was testing a combination of drugs to block several pathways at the same time.
Spurred on by promising results discussed in conferences and released in scientific journals (notably the Beacon trial, which published its results in 2019) by teams using drug combinations, her oncologist, Prof David Cunningham at the Royal Marsden Hospital in Chelsea replaced her chemotherapy with a drug to inhibit BRAF, encorafenib, along with drugs aimed at other pathways, a so called MEK inhibitor, binimetinib, and an EGFR inhibitor, cetuximab. (MEK is another gene, like BRAF, that is part of the cell’s internal signalling machinery, while EGFR is the gene for a receptor, a molecular switch on the surface of cells that receives growth signals).
Deborah suffered serious side effects including severe skin reactions, and even a temporary loss of vision. But the triple drug cocktail worked and as she wrote in the Sun: ‘My doctors were so amazed at my reaction to the drugs that I became a case study when the National Institute for Health and Care Excellence (NICE) were debating whether to make them available on the NHS.’
Subsequent studies have now suggested that for most patients the MEK inhibitor only has a marginal effect and NICE approved the combination of encorafenib and cetuximab last year.
But Deborah suspected she had particularly benefited from the third drug and one novel approach to investigate her hunch is to create an organoid of her tumour (developed by Prof Hans Clevers at the Hubrecht Institute in the Netherlands, these ‘mini organs’ are becoming widely used, for instance for COVID research).
Three years ago, Deborah heard a talk about the potential of organoids in cancer research by Dr Marco Gerlinger, who is an oncologist at the Royal Marsden Hospital and runs a research laboratory at the Institute of Cancer Research, ICR, London. ‘I turned to my oncologist David and said: “I want an organoid!”‘
Thanks in part to her persistence and enthusiasm, the ICR team got an organoid culture and testing study approved (‘patients like Deborah help us enormously,’ Dr Gerlinger told me). When Deborah needed another operation in Christmas 2020, a five-millimetre cubed sample of tumour was taken to be grown in the ICR lab.
Cancer cells were extracted from her tissue and embedded in a substance called a hydrogel, mimicking some of the conditions in the tumour, and fed growth factors in a tiny dome to encourage them to multiply.
The dream is to grow organoids which reflect the unique features of a patient’s cancer and have enough of them to test combinations of the hundreds of available anti-cancer drugs, one of the ways under study to create a personalised cancer treatment for each patient. But that would require an astronomical numbers of organoids, explained Dr Gerlinger.
To keep to manageable numbers, the selection of drugs has to be guided by genetic insights—in the case of Deborah, for example, they could explore if her tumour really is particularly susceptible to a MEK inhibitor, as her doctors suspected, given her genetic tumour test. ‘You need to focus the search,’ he said.
‘It grew fantastically well for a few weeks but then suddenly slowed down and stopped before we could start drug testing,’ said Dr Gerlinger. The cancer cells had gone into senescence (the loss of a cell’s power of division and growth). This happens in some of these mini-tumours and we are working on more sophisticated culture conditions to prevent it,’ said Dr Gerlinger. A few weeks ago, Deborah’s organoid died. ‘It is the only tumour I wanted to survive’, she told me.
Over the years, Deborah has been told she has ‘no evidence of active disease’, not once but twice, as a result of the triple therapy that was only expected to work for a few months. But this did not mean, however, that the cancer was cured. The disease recently returned, revealed by molecular markers which signal the presence of a tumour.
In April, two and a half years after starting the triple drug cocktail, her health went into reverse. ‘It was very scary. Everything happened very quickly.’
‘We talk about cancer evolution and I always knew that it would occur. But I underestimated the aggressive way in which it happened and the one thing you can’t control is where the tumours are.’
A fast-growing new tumour grew in a ‘hideous place’ near her liver so that it entwined her bile duct, prompting liver failure. She developed jaundice, her skin began to itch ‘like ants have moved in’, and her urine became the colour of cola.
Because the liver is the body’s detox organ, other kinds of drugs and chemotherapy were no longer an option. ‘I was definitely dying.’
In July 2021, Deborah had an emergency operation to insert a stent, her 13th operation. Though visitors were banned because of concerns about COVID-19 her mother, after much discussion, ended up at her bedside for three days to help her overcome a potentially life-threatening complication, sepsis, that developed after two weeks.
Deborah’s liver subsequently started to work sufficiently for her to restart standard chemotherapy, along with a drug called bevacizumab, which targets the network of blood vessels surrounding a tumour.
When I asked her how she was feeling, while on holiday in the south of France last summer, she was relaxed, ebullient and enjoying the sunshine. She had managed a walk to the beach earlier that day and joked: ‘I am still alive. That is the benchmark, right?’
In the light of that near-death encounter, she started to radically rewrite her second book, entitled How to Live When you Could be Dead, chopping 50,000 of its 80,000 words to add more details about how she has ‘been to hell and back.’
One of her most uplifting videos was one she posted as she danced in the garden with her mother Heather to the sound, appropriately enough, of the Bee Gees hit, Stayin’ Alive. Her spirit was indomitable and, after spending months in hospital, Deborah was already looking for another innovative treatment, one that will ‘put my cancer back to sleep’.
Chemo dancing whilst hooked up to life saving drugs is on! This cycle, kids are away, so mum has stepped up! She has literally been nursing me back to life for the last month through liver failure and sepsis – song couldn’t be more apt! Cancer is still happening! #stayingalive pic.twitter.com/YwlPxxIrNj
— Deborah James (@bowelbabe) July 20, 2021
Update: 16 May 2022
Deborah further inspired people across the world with the launch of the Bowelbabe fund, raising millions of pounds for Cancer Research UK, and on 12 May was awarded a Damehood by HM The Queen.
What a glorious afternoon to make memories for a lifetime! What an generous honour, to have William in my family home, with champange giving me a Damehood. Not sure life could get more surreal. But happy. @KensingtonRoyal you are welcome for tea at ours anytime! @BowelbabeF £5mil pic.twitter.com/oO4HuA9ZRO
— Deborah James (@bowelbabe) May 13, 2022
Sally MacDonald, Director of the Science and Industry Museum says
‘Dame Deborah James’ passion and commitment have touched every corner of the UK and beyond this past month. We have been so honoured to work with Deborah on such an important exhibition, in which her “rebellious hope” lives on. Our thoughts are with Deborah and her family.’
In addition to Deborah James, the other members of our exhibition advisory board are: Sir Paul Nurse, Director and Chief Executive of the Francis Crick Institute; Prof Paul Workman, Chief Executive and President of The Institute of Cancer Research; Prof Dan Davis, Prof of Immunology at Manchester University; Prof Charlie Swanton, co-director of the CRUK/UCL Lung Cancer Centre of Excellence, Group Leader at the Francis Crick Institute and Cancer Research UK’s Chief Clinician; Prof Karen Vousden, Cancer Research UK’s Chief Scientist and Group Leader at the Francis Crick Institute; Prof Daniel Hochhauser, a consultant medical oncologist at UCL; Terry Kavanagh, a long term lung cancer survivor, who sits on the Patient Panel for CRUK’S Grand Challenge; Natasha Lomax, who was diagnosed with Hodgkin’s Lymphoma (a type of blood cancer) in 2016 and a member of two panels at CRUK and one with UCLH; and Freya Parry, Head of Research Information, Communication and Engagement at Cancer Research UK.