Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Precision Oncology in the UK in 2017

Justin Stebbing, MA FRCP FRCPath PhD, Professor of Cancer Medicine and Medical Oncology at the Imperial College/Imperial Healthcare NHS Trust Charing Cross Hospital, London, UK;

Q: Science is universal but the practice of medicine varies widely by geography, economics, and culture. The United Kingdom is an advanced developed country with universal healthcare. How does your country approach the issue of precision or molecular oncology?

A: Great Britain and its major cities such as London are steadily becoming one of the leading healthcare destinations in the world, for patients, their families, and the best researchers and doctors there are. The combination of individualised but multi-disciplinary care, led by our academics at universities, medical schools, collaborations with industry, and critical mass is already prolonging quality and quantity of life and increasing the cure rate for most diseases, whether they affect men or women, young or old, and are common or rare.
Within this, there is an emerging paradigm of precision cancer care in which the use of molecular data at the point of therapy directly impacts patient treatment and clinical decision-making that is joined up between the patient and their medical team. This has already had a substantial, clinical impact on many aspects of healthcare services but up until now these have been surprisingly infrequent. Times are changing now. Oncology and cancer care is now at the frontline of personalised medicine, moving beyond the previous model of giving cancer therapeutics based on trials of largely unselected patients beyond a simple phenotypic marker. We are leading the way in utilising the molecular profile of an individual’s cancer genome to optimise their disease management – to treat the right patient, at the right time, with the right tumour, with the right treatment – including combinations of medicines, surgery and targeted radiotherapy. At the centre of this is the patient, with personalised medicine offering the promise of delivering safe and efficacious cancer treatments that are targeted, biologically rational, and avoid over- and under-treatment common with traditional chemotherapy, thus reducing toxicities associated with non-specific modes of action of chemotherapy.
Advances in personalized cancer care on the medical side includes well-established molecularly targeted therapies for patients with different sub-type of cancer including HER2-positive breast cancer, BRAF-mutant metastatic melanoma, EGFR-mutant or ALK-translocated lung cancer, and  BCR–ABL-translocation-positive chronic myelogenous leukemia. Clinical trials in the UK and London have led to many advances in treating these tumour types, turning them into long-term diseases that people live with, as opposed to dying from; often after treatment, the life expectancy of that person returns to normal. In London we are introducing large-scale genomic technologies at the point of care to aim to: i) catalyse discoveries in translational oncology and drive new research that aims to dissect selective responses to targeted, combination immunotherapies and chemotherapies, ii) identify new targets for which therapies are now in development and, iii) establish in real time, without delays, the right therapy for that person. Indeed, generated by the ability to generate increasingly complex molecular data directly from patient tumor and germ-line (the underlying genetics of a person) samples, the cycle of translating discoveries into clinical practice is accelerating at supersonic speed. Using cell-free DNA, which includes DNA derived from every cell type in a person’s cancer, on a rapid ongoing basis should allow this to occur. Research at Imperial College is establishing the role of cell-free DNA in diagnosis, prognosis, and prediction in order to best treat someone, as well as follow the course of disease. Remarkably, there is an infinite requirement for this, as tumours can change by the second and no two tumour cells are exactly the same. Indeed, the stupidest cancer cell is cleverer than the cleverest oncologist. A molecular arms race to keep up would seem the safest strategy but this has been constrained for too long by cost. There are now many new discoveries in personalised and precision medicine to live a healthier, longer life but until recently even in an exceptionally well-heeled practice, most patients are not willing or able to pay enough for the doctors to devote as much attention to each individual patient, to acquire the necessary equipment, to employ sufficiently well-trained staff, and to spend the time and effort on continuing education to make such a practice viable. Going forward, the vision for world-leading healthcare in London is that each patient now would be an individual – a one size fits all approach would be relegated. This isn’t just for cancer, it applies to every specialty from primary care and paediatrics, to intensive care, endocrinology, gastroenterology, cardiology, neurology, rheumatology and all of the surgical specialties alongside which true multidisciplinary care occurs.
Clinical trials, both led by doctors and others led by biotechnology and pharmaceutical companies are moving to the forefront of care in London, for devices and techniques as well as drugs. In conjunction with NHS England, the 100,000 Genomes Project aims to bring the benefits of personalized medicine to the NHS and make this an everyday reality across diseases. To make sure patients benefit from innovations in genomics, the British Government has committed to sequencing 100,000 whole human genomes, from 70,000 patients, by the end of this year. Successful delivery of the 100,000 Genome Project will enable us to achieve a number of ambitions including: i) to be the first country in the world to sequence 100,000 whole human genomes for the treatment of patients with rare/inherited diseases or common cancers, ii) to have high consent rates from patients and public support for genomics, iii) to have established world leading genomics services within the NHS, iv) to have educated and trained health professionals within the NHS in genomics and its applications for improved patient care and treatment, raising broad awareness and understanding of the advantages genomic medicine offers to patient care in the NHS, v) to be the home of world-leading genomics companies which will work in partnership with the NHS and its academic research partners, and vi) to have stimulated the development of diagnostics, devices, medicines and treatments based on a new understanding of the genetic and molecular basis of disease. This is the ultimate in what’s called bench-to-bedside translational approaches, and we are leading the way here.
Some patients taking part in the 100,000 Genome Project will benefit because a conclusive diagnosis can be reached for a rare/inherited disease or because a “stratified” cancer treatment can be chosen that is most suitable to their individual cancer. For most, the benefit will be in knowing that they will be helping people with similar diseases in the future through research on the genome and associated clinical data they generously allow to be studied. Their involvement in the project will allow an infrastructure to be developed, which in the future will support genomic services to be applied more widely to patient care in the NHS and across many clinical specialties. This will naturally lead to benefits in the private sector because the same individuals work in both sectors in London. For example, I personally work at Imperial College where I have my research laboratory; I work at Imperial College Healthcare NHS Trust where I see NHS patients; and I have a small clinic on Harley Street where I see some private patients and am involved in a number of trials of new immunotherapy combinations. Many of my colleagues are simply the best in the world at what they do. Recently, the UK Government’s Chief Medical Officer Professor Dame Sally Davies’ report called “Generation Genome” discusses how we can offer DNA testing as standard care in so many diseases like cancer (we are already using this to identify and treat different infection strains). In my laboratory we are studying the way our genetic code is turned on or off (or regulated) and the way a cell can turn into a specific type of cell including stem cells and cancer cells. We hope to use this to benefit our patients. The combination with artificial intelligence and machine learning to help us both store and analyse multiple genomes will be critical here.
Our scientists at Imperial College, Oxford and Cambridge (a so-called ‘Golden Triangle’), the Crick, University College London, King’s are leading the way in new technologies such as CRISPR. Many human diseases are caused by the mutation of a stretch of DNA, even with one change in a single nucleotide. Adapted from a primitive bacterial immune system, CRISPR does its handiwork by first cutting the double-stranded DNA at a target site in a genome and in doing so, gives us an ability to greatly alter genetic material as a new therapy for diseases. This has been used in London to understand early embryonic development and use stem cells more reliably to treat disease. Whilst the main aim is to improve the lives of patients, there are potentially many economic benefits for the nation and ultimately the world we live in. Some may be unexpected, built on new, as yet undiscovered technologies that will emerge and we need to be patient. But such benefits may be improved diagnostic tests, better tailored treatments, and development of new treatments and medicines. The role of diet, exercise, complementary medicine utilising techniques from hyperthermia to metronomic chemotherapy, acupuncture to anti-oxidants (as per my own pieces in the Lancet Oncology on the subject of complementary medicines) would be at the forefront of care here, not relegated to an afterthought. It would place the patient’s psychologic state of wellbeing at the centre of their outcomes (in many ways this is as important as the surgery or medicines); one without the other is sub-optimal. Finally, we aim to prospectively collect data here, own those data, and link phenotype such as behaviour and history to the genetics of the cancer or any disease, and the individual as a whole. In doing so, we aim to transform the lives of our patients and their families, disrupt the course of disease, and offer the very best healthcare in the world. This is occurring in real time now, and data generated should benefit patients and their families for decades to come.
Justin Stebbing’s contact info is included in the author affiliations at the top of this page.
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