The world’s first ‘Darwinian’ drug discovery programme specially designed to tackle cancer’s lethal ability to evolve resistance to treatment is to be launched in a state-of-the-art new building in London.
The Institute of Cancer Research, London, is to invest an initial £75 million in creating a global centre of expertise in anti-evolution therapies – which hold the promise of outsmarting cancer to improve cure rates.
Cancer’s ability to constantly adapt, evolve and develop drug resistance is what makes it so lethal – causing the vast majority of cancer deaths.
But scientists at The Institute of Cancer Research (ICR) aim to harness evolutionary science within a new Centre for Cancer Drug Discovery to ‘herd’ cancers with anti-evolution drugs and combinations. They believe this new approach can deliver long-term control and effective cures, just as comparable approaches have with HIV.
Senior scientists at the ICR argue that the traditional use of ‘shock and awe’ chemotherapy against cancer has failed because too often it has helped fuel ‘survival of the nastiest’ competition and evolution among cancer cells.
The new Centre for Cancer Drug Discovery will instead bring together world-leading researchers from very different disciplines across drug discovery and evolutionary science under one roof to create new resistance-busting treatments – coming together with the joint aim to overcome or redirect the whole process of cancer evolution.
The ICR is seeking a further £15 million from philanthropic donations to complete the new building and equip it with state-of-the-art instruments and computational technologies.
The building will house a series of pioneering projects including:
– Use of AI and advanced maths to ‘herd’ cancer like livestock so it is forced to adapt to one treatment by developing weaknesses against others
– Creating the world’s first anti-evolution cancer drug to slow down cancer’s ability to evolve and so delay its resistance to treatment.
– Devising innovative, multi-drug combinations that block several different cancer genes at once or that boost the immune system – as used to achieve long-term control or cures for diseases such as HIV and tuberculosis.
The ICR – a charity and research institute – is already the world’s leading academic centre for the discovery of cancer drugs.
In 2016 it became the first cancer research organisation in the world to place Darwinian evolution at the centre of its strategy for defeating cancer.
The ICR is taking a major step forward in putting that strategy into action by creating the new Centre for Cancer Drug Discovery and the world’s first drug programme that is dedicated to overcoming cancer evolution and drug resistance.
A major focus will be a new approach researchers are calling ‘evolutionary herding’.
ICR researchers have shown that it is possible to use artificial intelligence (AI) and advanced maths to forecast how cancers will react when treated with a particular drug.
By selecting an initial drug treatment, they have found they can force cancer cells to adapt in a way that makes them highly susceptible to a second drug or pushes them into an evolutionary dead end.
Herding cancer cells in this way through sequential use of cancer drugs could either eradicate the disease or turn incurable disease into a manageable chronic condition.
The ICR is also creating what researchers believe is the world’s first family of drugs to target cancer’s ability to evolve and become resistant to treatment.
These potential drugs are being designed to stop the action of a molecule called APOBEC to reduce the rate of mutation in cancer cells, slow down evolution and delay resistance.
APOBEC protein molecules are crucial to the ability of the immune system to adapt to different infectious diseases – but are also hijacked in over half of cancer types to speed up evolution of drug resistance.
Researchers hope that a new class of APOBEC inhibitors could be given alongside a targeted cancer treatment to ensure it can keep cancer at bay for much longer.
Latest ICR data show that APOBEC inhibitors can also increase the effectiveness of new treatments that use viruses as a form of immunotherapy to attack tumours.
Promising findings from the ICR’s drug discovery scientists have already shown that combinations of targeted treatments that attack cancer in multiple ways at once could have huge potential for preventing cancer from evolving resistance – using the same approach as in successful treatments for HIV and tuberculosis.
One approach that has shown promise in the lab involves combining three targeted drugs together to block drug resistance.
ICR researchers found that bowel cancer cells could evolve resistance in response to two targeted treatments but could be overcome with addition of a third.
Scientists at the ICR believe approaches like this could be a highly successful way of managing cancer and its spread to ensure good quality of life for longer – or to achieve cures through combination with exciting new immunotherapies and viral treatments.
The ICR’s pioneering new approach relies on bringing together drug discovery and evolutionary scientists into a single collaborative space – which is why it needs to meet the £15 million shortfall to complete and equip the Centre for Cancer Drug Discovery as soon as possible.
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
“Cancer’s ability to adapt, evolve and become drug resistant is the cause of the vast majority of deaths from the disease and the biggest challenge we face in overcoming it.
At the ICR, we are changing the entire way we think about cancer, to focus on understanding, anticipating and overcoming cancer evolution.
If we can raise a further £15 m to deliver our new Centre for Cancer Drug Discovery, we can bring together under one roof experts in cancer therapeutics alongside others studying evolution in animals, cells and individual patients, to create a new generation of cancer treatments.
“We will create exciting new ways of meeting the challenge of cancer evolution head on, by blocking the entire process of evolutionary diversity, using AI and maths to herd cancer into more treatable forms, and tackling cancer with multi-drug combinations as used successfully against HIV and tuberculosis.
“We firmly believe that, with further research, we can find ways to make cancer a manageable disease in the long term and one that is more often curable, so patients can live longer and with a better quality of life.”
But that research will need support and our new Centre will dramatically accelerate the progress we’re already making.”
Dr Olivia Rossanese, who will be Head of Biology in the new Centre for Cancer Drug Discovery, said:
“More and more cancer patients are living longer and with many fewer side effects through new targeted cancer treatments.
But unfortunately, we’re also seeing that cancer can become resistant very quickly to new drugs – and this is the greatest challenge we face.
“Within the Centre for Cancer Drug Discovery, we plan to deliver a drug discovery programme that is wholly focused on meeting the challenge of cancer evolution and drug resistance through completely new ways of attacking the disease.
This ‘Darwinian’ approach to drug discovery gives us the best chance yet of defeating cancer, because we will be able to predict what cancer is going to do next and get one step ahead.
“We’re especially excited by the potential of APOBEC inhibitors to slow down evolutionary diversity and drug resistance, and ensure our existing cancer drugs work for patients for much longer.
We believe this will be the first treatment in the world that rather than dealing with the consequences of cancer’s evolution and resistance, aims to directly confront the disease’s ability to adapt and evolve in the first place.”
Dr Andrea Sottoriva, who will be Deputy Director of Cancer Evolution in the new Centre for Cancer Drug Discovery, said:
“Artificial intelligence and mathematical predictive methods have huge potential to get inside cancer’s head and predict what it is going to do next and how it will respond to new treatments.
“Within our new Centre for Cancer Drug Discovery, we plan to use cancer’s survival instinct against it through an approach we call ‘evolutionary herding’.
By encouraging cancer to evolve resistance to a treatment of our choice, we can cause it to develop weaknesses against other drugs – and hopefully send it down dead ends and to its own destruction.
“With continued support, and by bringing cancer evolution experts together with our drug discovery colleagues in the new building, I believe we can help usher in a new era in cancer treatment.
There’s no reason why we can’t stay one step ahead of cancer and ensure it becomes a manageable disease in the future.”
Christine O’Connell, 46, from south west London, was diagnosed with secondary breast cancer in February 2018. She said:
“I was initially diagnosed with breast cancer in December 2012, aged 40.
After intensive treatment over the better part of the following year, I gradually regained a normal life.
I was fit and well, and nearly 5 years post-diagnosis, I thought cancer was well and truly behind me. “But in February 2018, I had a seizure.
A scan revealed a brain tumour, and I was diagnosed with secondary breast cancer.
I was in total shock – it was hard to accept how one minute you could believe you were cancer free, and the next be facing an incurable disease that could progress at any stage.
“I am lucky to be on a targeted therapy called palbociclib with side effects that are much easier to manage than chemotherapy, which allows me to have a relatively normal life.
It gives me hope that my cancer may be kept in check long enough for the next advances in treatment for secondary breast cancer.
Treating cancer as a chronic condition that can be managed on a long term basis may seem a modest ambition compared to efforts to cure it entirely, but for patients like myself this would be a significant victory.”
Find out more and help the ICR finish their new cancer drug discovery centre at ICR.ac.uk/DrugDiscovery
Source: The Institute of Cancer Research