Innovation in Oncology - Q3 - Aug 2018 by Mediaplanet UK&IE

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SEPTEMBER 2018 HEALTHAWARNESS.CO.UK

DR MARIAM JAMAL-HANJANI

DR ANDREW TUTT

PROFESSOR CHARLES SWANTON

A tumour is not a uniform mass; it can evolve over time P4

How DNA testing can personalise cancer treatment P6

How the UK can capitalise on its scientiﬁc talent P2

Innovation in Oncology

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The UK needs more clinical academics to compete with the USA Professor Charles Swanton Chief Clinician, Cancer Research UK

The UK has world-beating science talent. By offering MD PhD training for medical students in their 20s, we can innovate and advance oncology research, diagnostics and treatment, and benefit cancer patients, scientists, the biotech sector and the UK economy. “It may be controversial to say so, but UK science, though excellent, could be even better,” says Professor Charles Swanton, Cancer Research UK’s Chief Clinician. With a new approach to educating our clinical academics, we could take better advantage of the huge biomedical science opportunities in the UK, deliver innovative patient care, boost the UK’s biotech sector, generate more funds for use in the NHS and beneﬁt the UK economy as whole, according to Swanton.

Better training “First, we must capitalise on our talent,” says Swanton. He suggests that UK medical training could incorporate a PhD at medical school, mimicking the best MD PhD programmes in the USA. “The USA has combined MD PhD programmes, creating clinical academics at a rate of 5,000 a year. It gives them a ready supply of research talent at faculty level in clinical research centres and in the biotech and pharma sector.”

This compares with the UK, where medical doctors wanting to do research typically wait until their 30s. “By that time, they often have many other commitments including the completion of specialist training. It is so much harder with these commitments to give scientists the time required to fully train,” says Swanton. “A PhD within a combined MD PhD training programme at medical school gives medics a 10-year head start to develop the experience required to be a world-class researcher. Mimicking the US MD PhD programmes may be easier and more realistic. As Professor Gordon Stewart once said, ‘You train a scientist ﬁrst and a medic second’.” There are generous clinician scientist postdoctoral fellowships in the UK, and Cancer Research UK offers fully salaried clinician scientist fellowships where fellows divide their time between laboratory research and clinical practice. However, Swanton says, “We could be even more ambitious than this and train more clinical academics to aspire to be the best globally and compete with the USA.”

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How we can use our DNA to beat cancer Dr Nirupa Murugaesu Clinical Lead for Molecular Oncology, Genomics England

could lead to more biotech spin-out companies from research funders, which could create more employment and training for scientists and productive links with the academic sector in the UK. An even more vibrant biotech sector would help generate drugs and diagnostics technology that could be used by the NHS, and through royalty streams, generate more funding for academia,” he says. “Importantly, we also need longerterm capital investment to sustain fledgling biotech companies and develop and create long-term value for UK biotech. The last piece of the puzzle is that we need more individuals with dual training in academia and industry who can help spot and support innovative scientiﬁc technologies and develop viable business models to see them through to the clinic”. “We need a new model of science research funding, and it is possible, but only if we recognise that, in the UK, our talent is excellent - but it could be even better.”

Benefits of a new model An increased supply of clinical academics could take advantage of the wealth of opportunities for developing applications in areas such as genome editing and immunotherapy. “This

DISCLAIMER: BRISTOL MYERS SQUIBB HAS HAD NO INPUT TO THE CONTENT OF THIS EDITORIAL; THE VIEWS EXPRESSED ARE THE SOURCES' OWN

Linda Whitney

Taking a better look at the information inside us may be the way to fighting not just cancer, but a whole host of hereditary conditions. While genome sequencing may sound like something from Dr Who, you may be surprised to know that these technological advances are relied upon more and more in the NHS. Take the ﬁght against cancer, for example, using a simple blood draw and biopsy, so much more information than ever before can be derived about our body.

Cancerous cells ‘cloak’ themselves from the body’s immune system Recent scientific discoveries have found that some cancerous cells are able to ‘cloak’ themselves and evade the body’s immune system. Better understanding of complex mutations in some cancers, using genome sequencing, allows cancer doctors to better identify certain forms of cancers that are less able to avoid the immune system and those patients who might beneﬁt from additional or alternative treatments.

Scientists analyse the DNA of a tumour By taking a biopsy of a tumour and examining its DNA you can begin to discover its genomic makeup. When matched with the DNA found in your own blood, scientists simply subtract what appears as ‘normal’, to discover

the type of mutations the tumour harbours. This ability to drill down and study this tumour information is what Dr Nirupa Murugaesu, Clinical Lead for Molecular Oncology at Genomics England, believes will soon be more widely available in NHS Trusts. She recognises, however, that there are some changes to be made ﬁrst. “We need education and training within labs to ensure we are preserving our samples in a genomic-friendly way. “Advancements in technology enhances our knowledge in diagnosing different forms of cancer, how to treat those forms of cancer based on their genomic characteristics and even whether a patient could be at risk of developing that cancer again in the future. When having a genomic test, the tumour sample that is obtained during the patient’s cancer journey is studied, along with a consultation to inform you of the potential ﬁndings and agree your consent,” she says.

We can now identify patients who might be at risk of hereditary cancers “Thanks to advancements in genome sequencing, we can now identify groups of patients who may be at risk from hereditary cancers by analysing genetic markers and, with further research, identify more groups of people who may be at increased risk of developing cancer. With cancer, it’s all about catching the disease early enough to treat it.” Gina Clarke

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Research funders are a crucial link between academia and industry Survival from cancer has doubled in the UK over the past few decades, thanks to medical research. Further improvement rests largely on the promise of a new era of personalised medicine. This is where doctors first profile their patients and then offer targeted therapies that reflect the unique molecular fingerprint of a person’s tumour, rather than the ‘one size fits all’ approach of current medicines.

Scientists need support in knowing which of the many treatment development routes to take The abundance of potential avenues for drug development creates a unique challenge for those working in this ﬁeld, in trying to decide which to pursue. This is because a multitude of different targeted therapies to explore means increased development costs, which could ultimately lead to fewer drugs making it to patients. Companies need to invest wisely, and this is where research funders can lend expertise and support. We are uniquely positioned to lead cancer

innovation, with our commercial partnerships team providing a gateway for industry to access the most promising scientific discoveries. In this way, we assist scientists to progress their projects through industry partnerships, alliances and spin-out companies. At Cancer Research UK, we’ve moved to a more collaborative approach when it comes to translating our research. We identify areas or themes with a strong scientiﬁc foundation and the potential for developing drugs that could deliver meaningful patient benefit. We then bring together a team of

Tony Hickson Chief Business Ofﬁcer, Cancer Research UK

world-leading specialists, along with the drug discovery capabilities of our Therapeutic Discovery Labs and the industry expertise of a commercial partner. We combine the best minds in academic cancer research with the rigour and drive of industry, so that we can progress the most promising ideas for treatment without delay.

Research partnerships accelerate cancer detection and drug development As a charity and funder of cancer research, we’re often asked why we work so closely with industry. The results speak for themselves – these

partnerships have accelerated cancer detection and drug development and resulted in proven patient benefit. Through our collaborations, we’ve helped discover, develop and deliver many new tests and treatments, including the first ever PARP inhibitor for treating women with advanced ovarian cancer and the international standard of care for treating a form of brain cancer called glioblastoma. By working in partnership across both industry and academia, funders can accelerate and refine the development of potentially life-saving new treatments.

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Collaborative, years-long patient studies analyse the heterogeneity of tumours Collaboration is the way forward as multiple teams work together on new studies of cancer. Some tumours have many different parts – can identifying which tumours are the most variable give us some prognostic information to guide treatment?

aving always had an interest in science, Medical Oncologist, Dr Jamal-Hanjani, initially studied physics before medicine. She took time out of her clinical training to do a PhD and has, for many years, worked partly in clinical medicine and partly in research. She now specialises in lung cancer and is involved in two major studies, TRACERx and PEACE. Dr Jamal-Hanjani’s research looks at intra-tumour heterogeneity – the differences between one part of a tumour and another part of the same tumour. Centuries ago, pathologists looking down a microscope could see that not all parts of a tumour looked the same, but they had limited information about how those differences had evolved. The TRACERx study looks at tumour evolution in time, throughout the lifetime of a cancer, and in space, between different parts of the same tumour. Patients consent for the study team to take multiple samples when their tumour is removed – by having access to this very fresh tissue, gene sequencing can be done in much more detail than has been possible in the past.

A tumour is not a uniform mass; different parts evolve over time Dr Jamal-Hanjani explains that you can think of a tumour as a tree, made up of a trunk and branches. The trunk contains the genetic changes that occurred during the early development of a tumour and the branches are those that happened later on and affect only a smaller part of a tumour; however, it may be a small branch that drives the progression or recurrence of a cancer. Some tumours will have more or fewer branches than others. TRACERx follows patients for seven years. Blood samples are regularly collected and examined for circulating tumour cells and DNA in the hope that new biomarkers might be found. These biomarkers could predict a recurrence before it can be seen on a scan, thus allowing treatment to start earlier than is currently possible. Patients who have a recurrence of their cancer have a biopsy taken, so that it can be compared with the initial samples taken from the primary tumour. This can differ from usual practice as recurrences are generally treated as being the same ‘type’ of tumour as the original primary. Dr Jamal-Hanjani says that in the future,

it may become more acceptable that patients have a new biopsy at the time of recurrence as this may change their treatment. Analysis of the ﬁrst 100 patients has shown that, tumours with the most heterogeneity (i.e. more branches) in genetic abnormalities involving chromosomes, pose an increased risk of recurrence and may lead to patient death. If the study can develop tests to show which tumours are the most heterogeneous, this may be able to guide future treatment in a way that isn’t possible today. Dr Jamal-Hanjani also hopes to ﬁnd out the way in which chemotherapy affects the degree of heterogeneity, and how this might impact tumour evolution.

National post-mortem programme PEACE is a national post-mortem programme, and so far many TRACERx patients have been recruited into the study. Patients who have metastatic disease from any type of cancer are consented for tissue collection after their death. These are difficult conversations to have; Dr Jamal-Hanjani says that she is humbled by how many patients want to contribute to a study from which they won’t personally beneﬁt. Tissue is collected from cancer

tissue as well as normal tissue for comparison. Different teams use this data, working together rather than competing with each other – a collaboration that is not always the norm in the scientific world, where ‘publish or perish’ can be the motto. It is this collaboration, along with the longitudinal nature of studies like TRACERx and PEACE, which follow patients for many years, that will hopefully revolutionise the way we treat some cancers. Dr Jamal-Hanjani says that she is mindful of the selfless willingness of patients to be part of cancer research, without which, studies such as PEACE would not exist, and from which she believes future patients will benefit. Both TRACERx and PEACE are funded by Cancer Research UK. TRACERx is also funded by UCLH Biomedical Research Council, UCLH Experimental Cancer Medicine Centre and The Rosetrees Trust, and supported by the CRUK Lung Cancer Centre of Excellence, CRUK & UCL Cancer Trials Centre, the Francis Crick Institute and the UCL Cancer Institute. Dr Toni Hazell

Dr Mariam Jamal-Hanjani Senior Clinical Lecturer and Consultant Medical Oncologist, UCL Cancer Institute and UCLH

See more at healthawareness.co.uk

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How can we get gene therapy safely to the right place?

Dr Simon Newman Chief Scientiﬁc Ofﬁcer, NanoGenics

New delivery vehicles can help to get gene therapies to the right place in the body, making these treatments more effective, at a lower cost and with less toxicity.

ene therapy has changed significantly over time, says Dr Simon Newman, Chief Scientific Officer at the research company, NanoGenics. Dr Newman explained how cystic fibrosis (CF) was one of the fi rst diseases to be targeted by gene therapy. CF is caused by a defect in a single gene, so it seems obvious that replacing the mutated gene with one that doesn’t contain the mutation will treat the patient. Since then multiple other diseases, including cancer, have been identified as potential targets for gene therapy Dr Newman explains that the problem with gene therapy is getting the right amount of the

correct gene therapy safely into the correct cells. This problem has yet to be solved and we are still not close to a cure for even a single-gene disorder such as CF. How can we get the gene therapy to the right place in the body? Gene therapies have traditionally been delivered by modiﬁed viruses. Viruses naturally deliver themselves into cells, so scientists exploit this to use viruses to deliver gene therapies. This is risky, however. A major problem is that the body develops an immune response to the virus. This means that only one dose can be given, so there is no opportunity

to tailor the course of treatment to the patient, the disease or their response. Producing safe viruses to deliver gene therapy is costly – one gene therapy for lymphoma costs around £400,000 per patient. 2030% of patients who use this therapy (having failed all other treatments) will go into remission, but there is a signiﬁcant risk of toxicity which can be fatal. Using an artificial virus that acts as a delivery vehicle without stimulating the same immune response, allows treatment to be given more than once. It can be given directly to the place where it is needed (e.g. as an aerosol for lung disease or directly injected into the

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eye for glaucoma). It has a ‘lock and key’ mechanism – a ‘key’ on the surface of the artificial virus binds to a ‘lock’, which is only present on the specific cell type at which the drug is aimed. This allows the artificial virus to carry the gene therapy directly to the place in the body where it is needed.

deliver the gene therapy. Work is currently underway to use this for the treatment of neuroblastoma, a rare childhood cancer. Dr Newman hopes that the eventual outcome of this will be better treatments that can be given at a lower cost with less toxicity – a result that would beneﬁt patients and the NHS.

Working together to benefit patients This is an area where collaboration is important. Biotech and pharma companies who have gene therapies with no way of delivering them can work with companies such as NanoGenics, with the aim of using their artificial virus, LipTide to

Dr Toni Hazell

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How personalised treatment can improve patient care Adrienne had chemotherapy in 2005. Thirteen years later, she still lives with the effects and believes new technology could help others avoid her symptoms. Q. Can you tell me about your experience with breast cancer? A. I was diagnosed in 2005 and I was 48 years old. I had a long discussion with my oncologist about whether I needed chemotherapy. I had one positive lymph node, I was grade 3 and I would do anything to increase my chance of survival – so I did. It’s very difficult to talk about chemotherapy because human beings are exceptionally good at forgetting horrible experiences. It was just awful. Alongside the fatigue, fear of infection and sickness it induced, I had premature menopause so hot ﬂushes, sexual dysfunction... it was debilitating. I couldn’t work in my condition, which as a freelance scientist was tricky. I then went onto hormone therapy because my cancer was strongly hormone sensitive. Five years later, I developed metastatic breast cancer, which is incurable. I’m still alive eight years later, just on that treatment, and although we will never know, I do believe now that I didn’t need chemotherapy back in 2005.

Q. How has this affected your qualityof life to date? A. I believe my severe menopausal problems were as a result of the chemotherapy – which bought on such a sudden and dramatic menopause and totally shot my ovaries. I still have symptoms now, 15 years since the treatment. haven’t been able to work full-time since, due to the overwhelming fatigue and depression. Some people suffer from peripheral neuropathy – they lose feeling in their ﬁngers and toes, which, thankfully I’ve not experienced. But these are the potential longlasting effects of chemotherapy treatment.

Adrienne Morgan PHD Medical Research Scientist

With Prosigna testing, I would have been tested in 2005 and there would have been a genetic basis for strongly indicating whether I should have had chemotherapy. Allowing patients to decide whether or not they need to go through the hell of chemotherapy could lead to huge improvements in patient welfare in the long run. Alex van den Broek

Q. Why is personalised treatment so important for the future of breast cancer patients? A. Personalised treatment could inform patients properly on the value of chemotherapy treatment to their condition. IMAGE: GETTYIMAGES

Managing pain together Despite great advances in cancer treatments, people living longer with their disease, and the greater availability of drugs, pain management still remains a challenge. Pain can be misunderstood, under-reported and therefore under-treated, causing unnecessary distress. Through someone taking the time to listen, to truly hear another’s concerns, many people living with cancer can have their symptoms and worries addressed, feel better supported and have their pain better managed. To understand the visible and more hidden aspects of pain it is important to recognise the human dimension of pain, which has

four key elements:

1. Physical pain

2. Social pain

3. Emotional pain

4. Spiritual pain

“A disturbance in the relationship between the person and their body”

“A disturbance in the relationship between the person and their world”

“A disturbance in the relationship between the person and how they see themselves and relate to family/friends/others”

“A disturbance in the relationship between the person and their beliefs and what is important to them”

How do I relieve physical pain?

How do I relieve emotional pain?

How do I relieve spiritual pain?

Undergoing cancer treatments to shrink the tumour

Asking a doctor or nurse about support for those you may be concerned about

Getting support to continue doing the things that are important to you and your family

Not being afraid to acknowledge what is important to you

Seeking support from others who are also living with cancer

Doing things that help you feel better about yourself

Meeting others who have similar experiences through support groups

Choosing a friend to share your thoughts, feelings and concerns with

Talking to the Macmillan charity or a doctor or nurse about financial support

Keeping a diary or writing about feelings and emotions that are hard to share

Taking pain relief in the form of prescribed medications Finding comforting ways to be distracted from the pain Exploring creative coping strategies Undertaking physiotherapy and gentle exercise Experiencing complementary therapies, e.g. massage, reflexology, hypnotherapy, acupuncture

Getting help to talk to an employer and finding ways to adapt work conditions to suit you, if work is important to you

Being honest with your family and your children

Prisoritising people and things you value Talking to a trusted friend or a member of your clinical team Talking to a counsellor or a member of a pastoral care team Seeking religious/spiritual guidance or support with your values and beliefs

Getting help to talk to your children and family

While medicine has sometimes focussed on the more obvious forms of pain, there are less tangible forms of pain that also need addressing. By addressing the human dimension of pain and finding the time to hear the personal distress it causes, the person living with cancer may feel less isolated and alone. ADAPTED FROM MANAGING ADVANCED CANCER PAIN TOGETHER. QUINN, B. ET AL DIRECTOR OF NURSING FOR CANCER, BARTS HEALTH NHS TRUST, LONDON

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Patients to beneﬁt from new proton beam therapy centres

Dr Ian Barwick Chief Scientiﬁc Ofﬁcer, Rutherford Innovations

UK cancer patients who need high energy proton beam therapy treatment must often travel abroad to get it. Now, a new network of UK cancer centres will bring it closer to home.

n innovative oncology company is bringing high energy proton beam therapy treatment for cancer to within 90 minutes of 75% of the UK population. The Rutherford Cancer Centre South Wales in Newport is the UK’s ﬁrst high energy proton beam therapy centre, and is the ﬁrst of a network of eight proton beam therapy centres planned by Proton Partners International (PPI) for the UK. Dr Ian Barwick is the Chief Scientific Officer of Rutherford Innovations, the R&D arm of PPI. He says: “The Newport centre began treating proton beam therapy patients in April this year. The

technology to deliver high energy proton beam therapy is already being installed at our centres in Northumberland and Reading, which are both set to offer proton beam therapy next year. A fourth centre is under construction in Liverpool.” Proton beam therapy is not beneﬁcial for all patients. As such, mainstream cancer treatments such as radiotherapy and chemotherapy will also be offered at all of the centres. These will accept medicallyinsured private patients and selfpaying patients, as well as NHS patients should the centres be commissioned to provide proton beam therapy for them.

Saving the stress of overseas travel for patients NHS proton beam therapy centres are expected to open this year in Manchester, and, in 2020, in London. Until the opening of the Rutherford Cancer Centre South Wales, cancer patients had to travel abroad for proton beam therapy treatment. Proton beam therapy is often used to treat head and neck cancers in children, meaning that whole families often had to travel abroad for weeks at a time. Barwick says: “This can be a huge upheaval for the whole family. Once completed, our centres will offer an additional choice, where patients can have treatment ideally within 90

Simon Hardacre was the ﬁrst cancer patient to receive high energy proton beam therapy here in the UK, a treatment that can treat some cancers with fewer side effects than conventional radiotherapy.

imon Hardacre, the ﬁrst person to receive innovative high energy proton beam therapy in the UK, says, “I have been given intensive cancer care without suffering any gruelling side effects.” Simon, 56, chose proton beam therapy for his prostate cancer, with advice from Dr Jason Lester, Senior Consultant Clinical Oncologist at the Rutherford Cancer Centre South Wales, developed by Proton Partners International.

Proton beam therapy explained Proton beam therapy differs from conventional radiotherapy (which uses photons), and is very suitable

for certain tumours, with proton beam therapy treatment causing fewer side effects. Lester explains: “Proton beam therapy uses beams of protons to target cancers. Unlike conventional radiotherapy, protons stop when they reach the cancer, delivering most of their energy into the cancer rather than the surrounding healthy tissue. This may result in fewer side effects.” Proton beam therapy is especially useful for cancers at the base of the brain and the spinal cord in children, where conventional radiotherapy can cause brain or neurological damage, but proton beam therapy can also be beneﬁcial for other cancers such as prostate

cancer or those where tumours are in hard to reach places. Conventional radiotherapy can result in permanent rectal bleeding or diarrhoea Simon’s cancer was confined to his prostate gland, he was fit and motivated, making him a good candidate for conventional radiotherapy or proton beam therapy. “Simon chose proton beam therapy because it delivered a lower dose of radiation to the healthy structures around the prostate, reducing the chance of side effects,” says Lester. “As the prostate is adjacent to the rectum, in a few cases conventional radiotherapy can result in permanent

minutes of their home for 75% of the UK population, vastly improving the patient experience.” Research collaboration The centres will collaborate with universities and other global proton beam therapy centres in the advancement of research. Barwick says: “We will collect and share data. Larger datasets will provide better evidence to show when proton beam therapy may result in better patient outcomes in a broader range of cancers. In some European countries it has been shown that 10% of people receiving radical radiotherapy for cancer are likely to beneﬁt from proton beam therapy.”

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The company is working with the University of Liverpool to develop a new measurement system to enhance proton beam technology. It also has a pilot bursary for radiology students at the University of the West of England and Sheffield Hallam. Linda Whitney

Dr Jason Lester Senior Consultant Clinical Oncologist, Rutherford Cancer Centres

rectal bleeding or diarrhoea.” Before the treatment a saline-ﬁlled biodegradable balloon was inserted between the prostate and the rectum, so that radiation overlapping the edge of the tumour (essential to ensure the tumour is fully covered) passed into the balloon rather than the rectum. Simon could continue with his day-to-day routine Simon travelled the half-hour from his home in Woolaston, Forest of Dean, to Newport for this innovative treatment each weekday for four weeks. “Proton beam therapy cannot be felt by the patient and no injections, drugs or sedation are required. There were no immediate

side effects after each treatment, so Simon was able to carry on his normal routine, coming in for treatment between the school run and going to work,” says Lester. “Simon is the ﬁrst patient to be treated with high energy proton beam therapy here in the UK. So far, it looks to have been a success.” Linda Whitney

Find out more at therutherford.co.uk or ring 0800 210 0402

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Targeted therapy aims to outwit evolving tumours Studies show how cancer cells can evolve so as to resist and evade treatment. Now, trials aim to use this new knowledge to help ﬁght back. Professor Charles Swanton Senior Group Leader Francis Crick Institute, Cancer Research UK

pcoming trials that combine new knowledge about cancer evolution and immunotherapy could lead to major breakthroughs in cancer treatment. One of the reasons cancer is so hard to treat is not perhaps what you might expect: it’s evolution. New studies of the way cancer evolves are set to lead to breakthroughs in treatment. Professor Charles Swanton, Chief Clinician at Cancer Research UK, says, “Most of us think that evolution takes place over thousands of years. But it’s not true in all cases - tumours can evolve in weeks or even days.” This means that, over time, tumours evolve into a ‘patchwork’ of cancer cells in which different regions of a tumour have different genetic faults and behave differently.

Most of us think that evolution takes place over thousands of years. But it’s not true in all cases tumours can evolve in weeks or even days. Scientists call this phenomenon ‘intratumour heterogeneity’ and it explains why some cancers are difficult to treat, especially once they’ve started spreading round the body, where the secondary tumours can have a slightly different genetic make-up from the primary tumour.

Mapping tumour evolution Swanton was lead researcher on a Cancer Research UK study called TRACERx, the ﬁrst study to map the evolution of cancer in real time in immense detail. Researchers followed patients all the way from diagnosis through to either disease relapse or cure after surgery, tracking and analysing how their cancer developed. The study found that unstable chromosomes within lung tumours increase the risk of cancer returning after surgery. The ﬁndings reveal new insights into how tumours evolve and evade treatment, a leading cause of cancer death.

Ground-breaking trials Now, Swanton and his team are building on this research with two clinical trials, planned for 2019, involving patients with either lung cancer or melanoma. During the trials, immune cells, which target cancer cells with mutations found in every tumour cell, will be given to each patient. “This individually-targeted therapy takes personalised medicine to the limit,” says Swanton. “I hope the results will transform our understanding of cancer and how we treat the disease.” Read more at healthawareness.co.uk

Outcomes-based healthcare – an important opportunity for multidisciplinary care? Philip Poortmans President, European CanCer Organisation

here is good news to celebrate within cancer care. People are living longer, scientific and medical advances are offering innovative treatment options not previously possible, and professions across the cancer care continuum are developing increasing levels of specialisation. But this good news has implications for healthcare budgets. Continued improvement in cancer care may become stalled unless the health economics challenge of cancer care is met. Can the concept of outcomes-based healthcare provide a solution? Is it something to welcome, or should we treat it rather with healthy scepticism? It is timely for all practitioners and stakeholders in cancer care to reﬂect on these questions. Around 20-40% of healthcare spending is wasted There is a misallocation of resources in cancer care. A 2010 report by the World Health Organization estimated that 20% to 40% of all healthcare spending is wasted. It is also evident that the price tag attached to some products in cancer care – be they new medicines, medical devices, or other services – are not reasonably proportionate to the real beneﬁt they

Continued improvement in cancer care may become stalled unless the health economics challenge of cancer care is met.

Cancer care spending decisions must be evidence-based Investment and spending decisions in cancer care need to be more evidence-based and less based on ad hoc and politicised pathways. The opportunity for improvement offered by non-commercial innovation, such as enhanced multidisciplinary and multiprofessional care and the advances of all professional specialisms, deserve to be considered as candidates for investment by health budget holders on an equal footing to propositions put forward from the commercial sector. We could all usefully know more about:

provide over existing or alternative treatments. Furthermore, the largest investments by healthcare systems do not always go to the developments that will make the most notable differences in outcomes for the patients. Outcomes-based healthcare therefore addresses matters of real substance. But can it deliver on its promise, and make improvements in cancer care more sustainable? Perhaps it is still too early to tell. However, as a passionate advocate for better cancer care, I can say that I want it to work.

• What outcomes-based healthcare really means; • Its advantages and pitfalls; • Its impact and resonance for speciﬁc areas of cancer care. This is why we are putting the exploration of outcomes research, value-based healthcare and the tracking down of waste and inefficiency in cancer care at the heart of the agenda of the ECCO 2018 European Cancer Summit.

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What is being done to improve survival for patients with cancer? These drugs effectively un-mask hidden cancer cells, allowing their identiﬁcation and destruction by the body’s immune system. This highly selective approach means that normal cells are most likely not affected, resulting in little or no toxic side effects to the patient – a problem commonly encountered with conventional chemotherapeutic agents.

or many years, improvements in the medical treatment of cancer have come in small steps, but this is now changing, says Dr Christian Rohlff, CEO of Oxford BioTherapeutics. Following a PhD in pharmacology from Georgetown University, Dr Rohlff identified cancer as one of the biggest areas for future research and decided to devote himself to the development of a cure. Working at the National Cancer Institute in Washington DC was a career-defining period during which he decided to consolidate his work in oncology, having been personally affected by cancer in his family. For the first 20 years of his career, he has witnessed improvements in treatments that have given patients extra weeks or months of life. However, in the last five to seven years, new drugs are coming along that can provide benefits measured in years and, in some instances, allow patients to be cured. He describes the next decade as likely to be tremendously exciting as we witness a larger proportion of patients with cancer being cured. He attributes this shift in focus, from disease remission to complete cure, to a greater understanding of the role each individual’s immune system plays in preventing cancer cells from multiplying. Our immune system protects us from infections and other illnesses, including those involving the

abnormal multiplication of groups of cells, i.e. cancer. A compromised immune system has devastating effects, including an increased susceptibility to infections not normally known to cause harm – this is commonly seen in patients with leukemia, multiple myeloma and in the AIDS spectrum of HIV. Dr Rohlff explains that cancers ﬂourish by both suppressing, and hiding from, the immune system. Some cancers can manipulate the immune system’s defences The immune system includes CD4 and CD8 T lymphocytes and natural killer (NK) cells, which are very important for the body’s defence against pathogens, such as viruses and bacteria, and for tumour surveillance. They have proteins on their surface called checkpoints, which allow them to be turned on or off as needed. Some cancers, however, manipulate this cleverly designed system by using a molecular ‘switch’. By activating these checkpoint receptors and turning the immune cells off, the cancer effectively ‘hides’ from the patient’s immune system and avoids its destruction by the body’s defenses. Checkpoint inhibitors are a new class of antibody drug, which attach to the checkpoint receptor, turning the lymphocyte and NK cells back on, so that they can, once again, defend the body against the cancer.

In some cases, this will allow the patient to be cured. Checkpoint inhibitors are already in use for some cancers, including blood cancers such as lymphoma and cancers of the lung and kidney. Improving the success of checkpoint inhibitor drugs Current checkpoint inhibitors are generally used at a late stage in treatment, commonly in patients who have either relapsed or not responded to conventional treatment. They usually only work for around one-quarter of patients on whom they are tried. To overcome this, Dr Rohlff is working on a second generation of drugs in this class, which will hopefully be effective for more patients. By activating both T-cells and NK cells, these drugs undertake a two-pronged approach to help the immune system identify and ﬁght the cancer. One of the beneﬁts of this type of treatment is that the drug will only work on the immune cells that have been switched off by the cancer, and will therefore selectively target the cancer cells that are ‘hidden’ from the immune system. It is very likely that most non-cancerous cells elsewhere in the body won’t be affected and so toxicity should be limited. This is important, as up to 7.5% of deaths in cancer patients have been attributed to severe side effects rather than the disease itself 1 (O’Brien et al, British

Dr Christian Rohlff CEO, Oxford BioTherapeutics

Journal of Cancer, 2006). A recent study by Public Health England and Cancer Research UK have placed 30-day treatment mortality ﬁgures for systemic chemotherapy for breast and lung cancer at 3 in 100 patients (Wallington et al, Lancet Oncology 2016). Taken together, the benefits of checkpoint inhibitor drugs will hopefully mean that they can be used earlier in the treatment pathway, rather than as a drug of last resort. Checkpoint inhibitor drugs can cost hundreds of thousands Some current checkpoint inhibitor drugs are very expensive (in the hundreds of thousands of pounds) but Dr Rohlff is conﬁdent that the new generation will be deliverable at no more than the cost of current cancer therapies. Diagnostic biomarkers based on a number of patient and tumor characteristics are also being developed to identify, in advance, which patients will benefit most. This will further help drive down costs by avoiding treatment in patients for whom the drugs won’t work. Does this mean that we can start to talk about a cure? It is always difficult to say that a disease is cured when a drug is relatively new – no one has a

1: REFERENCE O’BRIEN MER, BORTHWICK A, RIGG A, ET AL. MORTALITY WITHIN 30 DAYS OF CHEMOTHERAPY: A CLINICAL GOVERNANCE BENCHMARKING ISSUE FOR ONCOLOGY PATIENTS. BRITISH JOURNAL OF CANCER. 2006;95(12):1632-1636. DOI:10.1038/SJ.BJC.6603498. 2: SOURCE WALLINGTON M, SAXON EB, BOMB M, ET AL. 30-DAY MORTALITY AFTER SYSTEMIC ANTICANCER TREATMENT FOR BREAST AND LUNG CANCER IN ENGLAND: A POPULATION-BASED, OBSERVATIONAL STUDY. THE LANCET ONCOLOGY, 2016; 17(9): 1203-1216. DOI:10.1016/S1470-2045(16)30383-7

crystal ball. We do know that there are patients with lymphoma, for whom all other treatments had failed, who are completely free of disease six years after treatment with checkpoint inhibitors. There is every hope that the future outcome will be an effective cure for some types of cancer. This second generation of checkpoint inhibitors is still at the research and development stage, with initial testing planned for the next three years. The relevant T lymphocytes and NK cells are being extracted from patients so that the drugs can be tested in the lab and compared to current treatments. If all goes well, they should be on the market three to ﬁve years after that, so patients could be beneﬁting well within a decade from now. This is a fast-moving field with the potential for exciting change in the relatively near, and increasingly optimistic, future. Dr Toni Hazell

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