Dr Irene Chong, Clinician Scientist at The Institute of Cancer Research, London, and a Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust
World-leading cancer researchers have revealed plans to create a new generation of ‘anti-evolution’ therapies, designed to combat cancer’s lethal ability to adapt and evade treatment.
Scientists have come together to identify cancer’s capacity to sidestep treatment by evolving drug resistance – the so-called ‘survival of the nastiest’ – as the single biggest challenge we face in defeating the disease.
On Friday 22 July 2016, experts at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust launched a roadmap for overcoming cancer evolution, setting out how powerful ‘big data’ analysis can identify game-changing new treatments.
Overcoming cancer evolution and drug resistance
Predicting how cancers will evolve and their escape routes from treatment will allow researchers to design state-of-the-art clinical trials, assessing the best ways of combining new anti-evolution therapies to benefit patients.
Cancers evolve and adapt much as animals and plants do in response to changes in the environment, or bacteria do when they become resistant to antibiotics. Patients may initially respond to cancer treatment, but they often then relapse as their disease evolves and becomes resistant.
The new vision represents the first major research strategy to place at its heart the need to overcome cancer evolution and drug resistance. Key elements of the new approach to outsmarting cancer include:
- predicting the path of cancer evolution from a single tumour sample, so doctors can see and counter-act cancer’s next move
- creating brand-new types of cancer drug that block the whole process of cancer evolution
- directing patients’ immune systems to evolve in response to changes in the cancer
- blocking off cancer’s escape routes by adapting therapy to evolutionary changes or treating patients with scientifically selected drug combinations
- tracking the movement of tumours in patients’ bodies with high-tech imaging and state-of-the-art radiotherapy.
Developing new precision medicines
The new research strategy, Making the discoveries: our strategy to defeat cancer, makes clear the benefits of investing in cancer research at the ICR and The Royal Marsden by setting a series of challenging targets for progress against cancer.
The ICR commits over the next five years to discovering a new drug targeted against a novel evolutionary mechanism and a new immunotherapy, as well as several other precision medicines.
The ICR and The Royal Marsden also pledge to deliver practice-changing clinical trial evidence of the benefits of innovative cancer treatment.
Drugs discovered at the ICR and developed with The Royal Marsden are already transforming the lives of patients – most vividly shown by prostate cancer drug abiraterone, which is benefiting hundreds of thousands of men globally.
The ICR and The Royal Marsden will also treat patients in clinical trials using the MR Linac – the world’s most advanced radiotherapy machine – to enhance delivery of radiation to tumours through real-time imaging.
And the partners are committed to taking new approaches to treatment, early diagnosis and prevention from the research stage into routine clinical practice across the NHS.
Blocking off cancer’s evolutionary escape routes
Among the research highlighted in the strategy is the work of Dr Andrea Sottoriva, a scientist in the ICR’s Centre for Evolution and Cancer.
Dr Sottoriva has discovered that cancers evolve over time in patterns governed by the same natural laws that drive physical and chemical processes as diverse as the flow of rivers or the brightness of stars.
His research raises the possibility that doctors could take clinical decisions on how an individual patient’s cancer will change, and what treatments should be used, by applying mathematical formulas to tumour biopsies.
Also featured is Dr Bissan Al-Lazikani, who is using computer modelling and machine learning to understand the complexity of cancers, and calculate the best way of scientifically combining drugs to block off cancer’s evolutionary escape routes.
And Dr James Larkin, a Consultant Medical Oncologist at The Royal Marsden and Reader at the ICR, is carrying out clinical trials of new forms of immunotherapy which are having lasting effects even against advanced cancers – as the immune system itself adapts and evolves in response to changes in the cancer.
'Staying one step ahead'
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “Cancer evolution is the single biggest challenge we face in creating better treatments for patients. We have seen some great advances against cancer, but so often we find that the disease evolves, becoming ever more complex and genetically diverse, and finds ways to resist the effects of therapy.
“With such a major, enduring, complex challenge, we need a concerted effort to shift our approach to cancer research, and to focus pretty much everything we do on anticipating, outpacing and overcoming cancer evolution. Our new joint research strategy fires the starting gun on a race against cancer evolution, as we aim to predict the disease’s behaviour in order to stay one step ahead.
“The ICR already leads the world in discovering new cancer drugs, and together with The Royal Marsden has pioneered advances in precision radiotherapy. We believe that by focusing relentlessly on cancer’s complexity and evolution, we can create a new generation of anti-evolution treatments that deliver even greater benefits for patients.”
Professor David Cunningham, Director of Clinical Research at The Royal Marsden and the ICR, said: “As the only NIHR Biomedical Research Centre dedicated solely to cancer, our mission is to translate the advances in discovery science into real benefits for cancer patients, and to continue to influence and change patient care on a global scale.
“The complexity of cancer is a constant challenge to not only developing effective treatments, but also those which bring our patients a good quality of life, with fewer side-effects.
“Our new strategy utilises an ambitious, patient-centred approach that recognises the complexity of cancer and will use 21st century tools to develop smarter, kinder treatments for both adult and paediatric patients, covering targeted clinical trials, precision imaging and radiotherapy, and new forms of surgery.
“By developing innovative treatments, diagnostics and strategies for prevention, we can deliver better outcomes and improved quality of life for patients at The Royal Marsden, across the UK and around the world.”
Read the full research strategy [PDF]