Cancer cells dying through the newly-discovered process of necroptosis. When the cells die in this way they lose their membrane integrity and take up red dye, turning them red.
In an important step towards personalised medicine, the findings from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) shed light on why cancer patients can fail to respond to some chemotherapy drugs and reveal a new way of targeting resistant tumours.
Until recently, it was thought cells could only die through a process called apoptosis. Because apoptosis is often blocked in cancer cells, drugs frequently don’t work, allowing tumour cells to grow and spread. In work published today online in the Molecular Cell journal, the team found some chemotherapeutics actually worked through a newly-discovered form of cell death, known as necroptosis.
Importantly, they found in the laboratory it was possible to activate a set of proteins and push cancer cells into this form of cell death, raising hope of new targeted treatments that could also kill apoptosis-resistant tumour cells.
Study author Professor Pascal Meier, from the Breakthrough Breast Cancer Research Centre at the ICR in London, said: “These findings represent a new line of attack in the fight against cancer. Chemotherapy has been around for decades but we have never understood how it kills cancer cells. This work shows not only that it can happen by two different processes, but how drugs can be developed to activate this newly discovered second cell-killing process in a much smarter, more effective way. We are at an early stage with this work but it could represent a new way of thinking about how we treat cancer patients in the future.”
The team was trying to find out how a class of chemotherapy drugs called topoisomerase inhibitors kill cancer cells. They identified for the first time how a number of key proteins involved in this process work together to kill cancer cells, finding that the chemotherapy drugs used necroptosis instead of apoptosis.
They discovered that the complex, or set, of proteins, could be switched on to effectively kill cancer cells. Because this cell-killing action is much more prominent in cancer than normal cells, it means these proteins could make an excellent target for new, more effective, targeted treatments, with fewer side effects for patients. It also means that patients whose tumours lack any of these proteins should not be treated with certain chemotherapeutic drugs.
Excitingly, a drug which targets one of the proteins in this complex, called SMAC-mimetics, is already showing promise in clinical trials. These results add further weight to the argument that SMAC-mimetics could be an effective cancer treatment for some patients.
Dr Julia Wilson, Head of Research Management at Breakthrough Breast Cancer, said: “This work is a major advance in our understanding of how cancer cells work, and how we can combat the disease. It suggests we can use chemotherapy more intelligently, and develop treatments which more precisely exploit this newfound weakness for the benefit of patients. We want to make sure that all breast cancer patients get the right treatment for them and this is a step towards that goal.”
For more information contact Richard Purnell in the Breakthrough Breast Cancer press office on 020 7025 2432 / 07778 682 001 or email firstname.lastname@example.org.
Breakthrough Breast Cancer
- Breakthrough Breast Cancer is a pioneering charity dedicated to the prevention, treatment and ultimate eradication of breast cancer fighting on three fronts: research, campaigning and education.
- Breakthrough Breast Cancer funds ground-breaking research, campaign for better services and treatments and raise awareness of breast cancer. Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good. Find more information at breakthrough.org.uk
- Breast cancer is the most commonly diagnosed cancer in the UK – nearly 48,000 women and around 300 men are diagnosed every year
- One in eight women in the UK will develop breast cancer at some point in their lifetime
- The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income, spending at least 90 pence in every pound of total income directly on research
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
- For more information visit www.icr.ac.uk