Space age genetic engineering offers hope for pancreatic cancer

Lynne Walker, Chair of the Board of Trustees of the charity Pancreatic Cancer UK, knows that she is very lucky indeed: she is alive.

Pancreatic cancer affects nearly 10,000 people a year in the UK, and five years later, only 7 per cent of these patients are still living. This compares with 80 per cent survival rates for breast cancers and other formerly highly lethal diseases. There has been virtually no improvement in the survivability of this kind of disease in 40 years.

Like most afflicted by this terrible type of cancer, Lynne was diagnosed almost by accident, in 2009 after she returned from a long-distance business trip complaining of exhaustion and a bad back.

She’d been pestering her GP for months and she had been investigated for a possible gall bladder complaint, but she was told there was nothing wrong. “I was running a successful management consultancy and I didn’t pay much attention to my aches and pains,” she reflects.

Lynne

Then, soon after she got back from Australia, feeling more than usually jet-lagged, she got up one morning to find she had turned completely yellow: it was an acute case of jaundice, in combination with the other symptoms, a clue as to what was really going on.

“This looks very serious,” her GP said, “I think we should call an ambulance.”

The penny had dropped at last and a specialist told her that she had a 50/50 chance of making it. She spent six months in hospital, during which she suffered sepsis, multiple organ failure and artery collapse, and nearly died several times.

She emerged, very much alive but as she says with a twinkle in her eye, “organ light,” the surgeons having saved her by chopping out half the diseased pancreas her gall bladder and duodenum and re-plumbed the rest– an option available only in a very few cases.

Often too late for surgery

The disease is especially hard to diagnose in part because of where the pancreas is located, deep within the body. It is hidden away behind the stomach and in front of the spine. Its function is to produce insulin, and other juices that help with digestion.

Location alone means that the disease is almost always advanced when it is first spotted, usually by accident as in Lynne’s case. It is especially nasty because it starts to metastasise, or replicate itself uncontrollably, before the tumour is big enough to be spotted on a CT or PET scan.

It is often too late for surgery. Conventional chemo and small-molecule targeted therapies are not effective, and the search is on to find a more reliable way of treating this most intractable of diseases.

Prof Nick Lemoine, the distinguished cancer research scientist who is director of the Barts Cancer Institute, is leading a three year research project to find a treatment using state of the art immunotherapy.

As explained in an earlier post, this means helping the body’s immune system to knock out the cancer cells, rather than seeking to poison cancer cells with the blunderbuss of chemotherapy.

Lemoine, who has a colourful turn of phrase as well as the most profound understanding of molecular biology, asks whether I have ever eaten sweetbread, that tasty morsel occasionally served up as a side-dish to a Sunday roast.

Prof Lemoine

A healthy pancreas is squashy like a lightly grilled sweetbread, explains Prof Lemoine, but a cancerous one is hard and gritty. Somewhat graphically, he explains that when you cut one with a scalpel, it feels like cutting an unripe pear. “You can hear the crunch as you go through…”

That hardness is due to fibrous tissue — a kind of Kevlar vest which neither chemo, nor the immune system’s killer T cells, have been able to penetrate effectively. It’s simply impossible to get in.

Cutting edge technology in virology and immunology

The solution is space age genetic engineering, drawing on cutting edge technology in virology and immunology.

The first step is to identify and build the kind of T Cells that will bind naturally to the antigens, the markers on the surface of the cancer cells. These specially engineered cells are called Chimeric Antigen Receptor (modified T) or CAR-T cells. They are brewed up in the lab using the patient’s own cells, then re-injected into her bloodstream.

The treatment will also deploy a class of viruses that target tumours. Astonishingly, research led by Prof John Marshall at Barts shows that part of the foot and mouth virus is exquisitely effective in seeking out and destroying cancer cells – the kind of serendipitous discovery that can lead to breakthrough medicine.

The virus creates a powerful danger signal that stimulates the immune system.

The third element of the therapy is to use known agents to pipe this cocktail of agents into the tumour by opening up the blood vessels that feed into the pancreas.

As Lemoine puts it, the overall effect will be to create a “weaponised T Cell” that punches through the Kevlar shield and goes to work on the cancer cells. “They will have nowhere to hide,” he says, looking like a medical version of Clint Eastwood tracking down an especially malevolent villain.

If this sounds futuristic, it is: the study alone will take three years and the resulting therapy will be exceedingly expensive and a long way from being generally available to patients. The objective is to get a treatment ready for clinical trial where its impact on patients can be properly evaluated before taking a drug to market.

But it is the start of a systematic and scientific attempt to treat a disease that has long gone ignored. Relatively low incidence and high mortality has made it unattractive for drug companies to invest in finding a cure, and sadly few people have survived long enough to become the kind of high profile, celebrity ambassadors that breast and prostate cancer have attracted.

At last, the disease is being given the attention it deserves.

To give the last word to Lynne, one of the rare survivors:

“I owe my life to the excellent treatment I received on the NHS. Yes, I had a positive mental attitude throughout, but I am aware that luck played a very large part in my survival.

“It cannot be acceptable in this day and age that for a disease like this we have to rely on luck. We need early diagnosis and we need treatment options.”

Prof Lemoine’s pioneering project is showing the way.

Why me, doctor?

“Why me, doctor?”

“Well, I’m sorry to tell you, you’re too fat.”

Even the most insensitive oncologist is unlikely to answer the question so bluntly. Your cancer could be hereditary, triggered by a virus or (more likely) caused by a random genetic mutation.

But it really could be because you are overweight.

Cancer Research UK’s ongoing campaign against obesity has been impossible to avoid: http://bit.ly/2FlSixF – as it seeks to ram home the message that being overweight is the second biggest preventable cause of cancer, after smoking of course.

Obesity is a factor in 18,000 cases of cancer a year

As a population, we understand that booze and especially fags cause cancer, but burgers and fries have hitherto escaped their fair share of the blame. In total, 5 per cent of cancers in the UK have a link to obesity.

If 5 per cent does not sound like a big number, think again: that is 18,000 cases a year.

The month-long campaign has involved billboard and print advertising, a social media onslaught and other attention-grabbing tactics.

Volunteers have gone to the high streets of middle England to hand out cigarette packets, asking passers-by what they think is the second biggest preventable cause of cancer.

People in Aylesbury, for example, were astonished to find the packets contained chips, and to learn that 13 different cancers in the UK have a strong link to obesity.

“It is a shocking and surprising message,” comments Emma Shields from Cancer Research. “We have a duty to tell people — and most people, after they have got over their surprise, want to know ‘why haven’t I heard this before.’”

Beyond the headlines, Cancer Research is hoping that the campaign will influence government policy around junk food: the charity wants TV advertising for this kind of food to be banned before the 9pm watershed.

The risk of obesity is especially acute for younger people, so-called millennials whom Cancer Research says are eating much less healthily than their parents, and are going to be fatter as a result.

Four out of ten cases of cancer in the UK are avoidable

The bigger picture is that some 40 per cent of UK cancer is caused by people’s lifestyle, namely smoking, drinking and eating too much of the wrong kind of food.

Yet a comparatively small amount of the healthcare budget for cancer is spent on education and prevention and awareness – most of it goes on the kind of sophisticated and therefore expensive new drugs described in my last post (monoclonal antibodies, immunotherapies and the like.)

New treatments can deliver spectacular results, but only for a relatively small number of people, compared to the numbers who might avoid cancer altogether by changing the way they live.

The need to invest in prevention, education and awareness

“Education and awareness are simply not good enough,” says one oncologist, venting his frustration about public policy priorities. “Especially when we know we can take big steps to prevent the disease by encouraging people to stop smoking, moderate their alcohol consumption and eat a better diet.”

Of course, this is a highly charged subject, as the emotional reaction to Cancer Research’s alleged “fat-shaming” has made only too apparent.

It is fair to say that the connection between being overweight and getting cancer is not straightforward. Not all people who are obese are going to get cancer, just as many perfectly trim people are going to get cancer. And whatever the cause, no one deserves to feel shamed or blamed as a result of the diagnosis.

Yet Cancer Research deserves to be praised for venturing into this controversial territory.

If their warnings encourage just some of us, let alone a whole generation of millennials, to eat a balanced and healthy diet, that has to be a good thing. And if it in any way puts the brakes on the incidence of avoidable cancer, that would be an outstanding outcome.

Prof James Spicer – dispensing optimism

Prof. James Spicer has come to the pub directly from his twice weekly lung cancer clinic at Guy’s gleaming cancer centre near London Bridge.

“The average person would expect me to come straight out of clinic and order a triple vodka to recover,” he jokes. “But the reality is not like that at all. I feel that in a clinic like ours I’m going around dispensing optimism.”

As if to demonstrate that it wasn’t too bad a day, he orders a pint of bitter rather than vodka, and gets straight to the point.

“People come to us thinking they have an irredeemable death sentence. But that is no longer the case. We are talking about options, which treatment will be best for you in which order, how soon we will know if it is working, what will we change to if it doesn’t work.

“In short,” he says, “there is so much to discuss and be optimistic about.”

jamesspicer

Look at survival rates for different types of cancer, it is undeniable that lung cancer is one of those diseases that still carries a relatively poor prognosis – and that has not improved significantly over the years, unlike for blood or breast cancer, for example.

Lung cancer is especially chaotic and complex

There are many reasons for that, not least the complexity of lung cancer. Unlike certain leukemias or lymphomas, for example, which are caused by one genetic malfunction, the kind of lung cancer contracted by a smoker is typically “chaotic,” meaning there are dozens of cancer genes doing their evil work. This has made lung cancer especially resistant to traditional forms of treatment.

The reason for Prof Spicer’s optimism is the new science of immunotherapy, whereby the body is encouraged to use the powers of its own immune system to attack and destroy cancer cells. This is distinct from old-fashioned chemotherapy and the targeted therapies that tackle cancer-causing genetic abnormalities.

“I’ve been in my post eleven years, and when I started, nobody had really heard of immunotherapy,” Spicer explains. “I’d go to a big cancer conference and there’s be a small room at the back dedicated to this weird new field. Now it’s more like 70 per cent of all the new data presented relates to immunotherapy.”

Prof Spicer has an unusual background for a cancer specialist. After studying at Oxford, he worked for a spell as an investment banker before returning to study medicine. He now has a job that requires crossing from one end of the car park (the science labs) to the other (the clinic), straddling both research (into new forms of treatment) and patient care. He is Professor of Experimental Cancer Medicine, King’s College London, and Consultant in Medical Oncology, Guy’s and St. Thomas’ Hospitals London, UK

Immunotherapy holds out the promise of revolutionary benefits

Immunotherapy has already delivered revolutionary benefits for melanoma and other diseases, and offers huge hope, not just for lung cancer but also other intractable diseases like pancreatic cancer. It’s not without its side effects, and is far from a panacea, but Dr Spicer is excited about its potential.

The revelation came around the turn of this century, when scientists realised that “combination therapy,” putting together cocktails of poisonous chemo, was something of a dead end (forgive the pun). At the same time, the biology of cancer was becoming better understood.

One outcome was so-called monoclonal antibodies, drugs that go after specific cancer cells. They are designed to go in hard by targeting a single genetic abnormality and as a result can be more effective than the blunderbluss of chemo. Herceptin, used to treat breast cancer, is an example of one these targeted therapies.

After chemo and targeted therapy, immunotherapy is the “third way” that has come into its own in the past five years. The magic of this kind of treatment is that it is targeted not at the cancer, but at the immune system.

Normal cells are successful in sending signals to the immune system. When there is something wrong, the system switches on and puts things right. With Darwinian deviousness, cancer cells are often successful in faking things so that the immune system is tricked into thinking there is nothing amiss.

Interrogating cancer cells more effectively

“Cancer cells have mechanisms to push away immune cells,” Spicer explains, clearly slowing down as he knows he is talking to a layman. “Now we can block those mechanisms so that the immune system can wade in and do the job we want it to do.”

This is the new paradigm: the immune system’s very own T-Cells trained to interrogate cancer cells more effectively than they could do the job on their own.

There is a paradoxical hope for those with nasty, chaotic lung cancer caused by smoking: this presents a better target for immunotherapy drugs, than other types of lung cancer where the diseased cells more easily pass themselves off as normal.

There is hope elsewhere, as more than 50 per cent of lung cancers now have a “biomarker” i.e. a genetic malfunction that is understood, recognisable and treatable – either by the new immunotherapy or drugs targeted at specific variations (e.g. the EGFR marker).

In future posts, we will examine the science in more detail. For now, here is Prof Spicer’s message of realism balanced by hope:

“Don’t get me wrong,” he says. “Lung cancer is still a pretty grim diagnosis, and for every poster child patient who is doing spectacularly well on the new drugs, there are lots of patients who have horrible diseases that don’t respond to anything. But there is is enough going on to be really optimistic about, and it’s really important to me that patients pick up on this positive psychology.”

This is a sentiment we can all raise a glass to.

Cancer — the uncertainty factor

What are my chances?

From the moment you are diagnosed with cancer, you are plunged into a world of uncertainty.

In the first hours and days after the diagnosis, you may have no idea how advanced or aggressive your cancer is. In due course, typically over a period of weeks, your disease is tested and evaluated, “staged” according to the jargon.

This is typically a period of torturous uncertainty, when you have to wait for your test results for what feels like an eternity, not knowing how bad things are, and imagining the worst.

Layer on the experience of dealing with a big bureaucracy like the NHS, and it is no wonder that the patient often feels lost and alone.

Once the doctors put a label on it, saying you have this or that kind of cancer, and it is at stage one, two, three or four, you will be told what your treatment options are. For solid cancers, this could include surgery followed by chemotherapy; for blood cancers, you might go straight to chemo or be put on a “watch and wait” regimen.

A view from Prof Arnie Purushotham of King’s College

At this point, according to veteran breast cancer expert Prof Arnie Purushotham of King’s College, London, the patient typically says, “thank you, what are my chances?”

There is no easy answer to that question.

“You can look at the trials out there and you can extrapolate from a mass of data and say well, you know, you have an eight or eighty per cent chance of being alive in ten years.”

But the reality is that this kind of information doesn’t tell you what is going to happen to you.

Patients are not statistical data, but rather living, breathing individuals, with hopes and fears as well as bloodcounts and tumour markers – and however much you might want to study the alarming charts on the internet showing survival rates, the advice from Prof Purushotham is – don’t give way to the temptation.

Arnie Purushotham

These data are useful to the specialist, but terrifying and unhelpful for the individual patient.

Not knowing is the worst thing.

Not knowing is the worst thing. Once you have an idea what your treatment is going to be, no matter how invasive, the patient often comes to terms with it.

There may well be a rollercoaster ahead, but at least you are in the system, with a plan of action and a timetable, and you are surrounded by people who are there to look after you.

But, even if you are cured or told you are in remission, for the rest of your days you will live in fear that the cancer will come back.

With every year that goes by, you will be tempted to open a more and more expensive bottle of champagne. But a voice inside will always be saying: not so fast. With time, the chances of recurrence go down, but no doctor is going to give you an absolute reassurance.

How can the system help patients deal with this?

Doctors can do more to eliminate uncertainties that arise because of the medical process. At many clinics now, for example, there is a big effort to get tests done and results communicated on the same day.

That may be a very bruising experience for the patient, but at least the terrible waiting is removed.

Straightforward communication from doctor to patient is also key. Honest reassurance, when it can be given, is always welcome, together with the recognition that whatever confusion, anger and distress you might be feeling, is entirely normal.

There is some consolation in realising that you are not the first to go through that gamut of emotions. In fact, millions of people have been on the same journey.

Thanks to Prof Arnie Purushotham, professor of breast cancer at King’s College London, for his valuable time. See his full CV here:

https://kclpure.kcl.ac.uk/portal/arnie.purushotham.html

https://www.guysandstthomas.nhs.uk/our-services/consultant-profiles/cancer/arnie-purushotham.aspx#na

 

Thank you!

Thank you for your tremendous feedback to this blog since it went live earlier this week. A lot of people have dropped a note to say they like the interview with Lesley Fallowfield. Here is a great response from a leading oncologist:

Lesley Fallowfield’s influence has been profound, and formal teaching of communication skills is very much more widespread now than it was when I was a trainee. But still the emphasis is on oncologists, cancer surgeons, specialist nurses – that is, cancer specialists. We still hear horror stories from patients about how they first hear of their diagnosis, from non-cancer specialties like general medicine. Too many clinicians fear breaking bad news (new diagnosis, relapse and so on) – I’m not saying it is something to be relished, but doing this difficult job well can be just as much a rewarding challenge as many other professional activities we regularly perform.

This is a topic I will return to in future posts.

Meanwhile, it has been a busy week for cancer news. I pay tribute to Nicola Mendelsohn, head of Facebook in Europe, for coming out with the fact that she has incurable blood cancer:

https://www.standard.co.uk/news/uk/outpouring-of-support-for-facebook-europe-boss-after-revealing-cancer-diagnosis-a3758011.html

Nicola has been put on the “watch and wait” regime which means that the doctors won’t do anything about her disease until, and if, progresses. Having “been there, done that,” with almost but not quite exactly the same diagnosis, I have to commend her courage and to wish her well as the years go by.

There was good news for Nicola, me and others with blood cancers: superb results from new trials. See http://www.bbc.co.uk/news/stories-42920045

The other “c-word” in cancer is of course cure, and there seems to be a real hope that some diseases can be kicked into touch for long enough to be classified as cured.

 

Professor Dame Lesley Fallowfield: the science and art of cancer communication

There is something scary-sounding about Professor Dame Lesley Fallowfield’s job: she is a psycho-oncologist.

We all know what an oncologist is, but the word psycho conjures up the image of the shower scene in Alfred Hitchcock’s film of that name…but in the flesh, Lesley Fallowfield is not at all frightening.

Lesley has the reassuring but firm manner of the nurse that she once was, coupled with the authority that goes with being a pioneer in studying the emotional and psychological aspects of the cancer experience.

Now professor of Psycho-Oncology at the University of Sussex, she has personally trained many hundreds of leading oncologists in how to communicate better with their patients, and is thus the ideal first person to be interviewed for this new blog.

Dame Lesley

Sitting in the basement of the elegant Royal Society of Medicine in London’s West End, she explained to me how she found her way into this professional niche. After she had completed her training as a nurse, she studied for a BsC in experimental psychology and neuroscience, and then a PhD. The defining moment in her early career came when she visited a friend at the Royal Marsden hospital in London. The friend was suffering the after-effects of an early bone-marrow transplant, and was very poorly indeed.

Continue reading “Professor Dame Lesley Fallowfield: the science and art of cancer communication”

Why communications makes the cancer experience less awful

Years after the diagnosis, I was sitting in a clammy hospital chair, at last undergoing the tedious process of chemotherapy, poisonous goo dripping into my bloodstream. It wasn’t anything like as bad as the doctor had predicted: I barely felt sick and my hair didn’t even fall out.

I found myself reflecting on the connection between my day job – advising companies and individuals on how to communicate, often during times of crisis – and what I was going through. How should people talk to you when they know you have cancer, and how should you talk to them?

The first rule of professional corporate communications is to divide your audience into stakeholders: categories of people who matter to you in different ways. For a big company, these would include your shareholders, employees, customers, regulators, the media, all requiring a subtly different but fundamentally consistent message.

Continue reading “Why communications makes the cancer experience less awful”