Stratified medicine means looking at large groups of cancer patients to find ways of predicting which treatments cancers are likely to respond to.
It involves looking in detail at the cancer cells and their genetic make up. Researchers want to find out if some treatments are more likely to work in cancers that have particular changes to their genes.
This is one step towards personalised medicine. Personalised medicine uses genetic and other information to diagnose and treat disease.
Once we have carried out research with large groups of cancer patients, we might be able to predict response to treatments. Then we hope we will be able to tailor cancer treatment very precisely to an individual person’s cancer.
Cancer Research UK's Stratified Medicine Programme
James Peach, Director, Cancer Research UK Stratified Medicine programme: Many of the next generation of cancer treatments will only work in people whose cancer is driven by a particular gene or protein.
We need ways to routinely group, or ‘stratify’ patients as part of their treatment. Cancer Research UK’s Stratified Medicine programme aims to help the NHS prepare for this exciting new way of treating cancer, and provide researchers with intelligence about how treatments work
Voiceover: Launched in 2011, Cancer Research UK’s stratified medicine programme will operate from 7 clinical centres and 3 genetic technology centres across the UK.
St James’s University Hospital, in partnership with the University of Leeds, is one of these clinical centres. Here, patients with a range of cancers are asked if they want to take part in the programme. The programme is initially focusing on people with breast, bowel, prostate, lung, and ovarian cancer, and melanoma.
If they agree, a sample of their blood is taken, the DNA extracted, and stored for later analysis. This gives researchers a sample of ‘normal’ DNA as a reference.
After the cancer patient has had surgery or a biopsy, a tissue sample is sent to the hospital’s pathology lab, where it will be specially treated to protect the DNA inside.
The tissue sample is sliced into wafer thin sections, which are rolled up and placed into a plastic tube. Then they are sent off for genetic analysis to the Institute of Cancer Research and the Royal Marsden hospital’s joint laboratory in Sutton – Leeds’s technology partner in the programme.
Here, the DNA is extracted from the sample and then run through powerful DNA sequencing machines to read each tumour’s unique genetic code.
Information about key mutations in the tumour is sent electronically back to Leeds, where it’s linked to the patient’s medical records. This information is also stored in a central database to help guide future research.
Although this won’t influence the way the patient is treated – at least in the short term – the resulting data will be absolutely vital to allow doctors and researchers to improve the way patients are treated in the future. So tomorrow’s cancer patients will benefit from the results of today’s research.
James Peach: It’s absolutely vital that the NHS starts thinking about how genetically stratified treatment will work in practice. Our programme aims to enlist around 9,000 patients to help us make genetic testing a routine part of NHS practice, as well as providing an unprecedented source of data for researchers, to help them beat cancer.
In the first part of the programme (SMP1), researchers collected samples from around 9,000 people with different types of cancer. They looked at the different genetic changes (mutations) in the samples, and this information will be used for future research.
This study has led to the next part of the programme, called SMP2. This is testing for genetic changes in non small cell lung cancer. The people in the study have part of their tumour and a blood sample sent for analysis.
The researchers will look for 28 different genetic mutations. Based on the mutation found, patients might be able to take part in the National Lung Matrix trial. This is looking at giving treatment depending on the genetic mutations in the lung cancer cells.
How doctors decide on treatment
Currently doctors decide on your treatment by looking at:
- your type of cancer
- where it is in the body
- the size of the cancer
- what the cancer cells look like
We know that this works for many people, but not for all. So scientists have been looking in detail at the biology of cancer cells. They've found that some cancer cells have particular proteins in the cell and others don’t. Or sometimes, that cancer cells have far more of a particular protein than healthy cells.
These differences between cells are caused by changes in the cancer cells’ genes. So you might hear people talk about genetic testing in relation to stratified medicine or personalised medicine. This means testing the genes in your cancer cells, not your normal genetic make up.
How these new treatments work
Scientists are most interested in cell proteins that work as messengers within and between cancer cells. For example, a particular protein might tell cancer cells to divide so that the cancer grows.
Researchers are now developing drugs to target and block these messenger proteins. The idea is that blocking these proteins will stop cancers from growing and spreading. But the targeted drugs are not suitable for everyone. They only work on cancers that have the protein they target.
Many of the newest cancer drugs target proteins on or inside cancer cells. For example, if you have breast cancer your doctor tests your cancer cells to see if they will respond to the biological therapy drug trastuzumab (Herceptin). Only breast cancers that test strongly positive for the HER2 protein are likely to respond well.
Access to treatment
So now we know that two people with the same type of cancer might have differences in their cancer cells. These differences mean that the cancers will respond to different types of treatment. The medicine that targets a particular cell change won’t work if your cancer doesn’t have that cell change.
Being told you can’t have a particular treatment might not sound like a step forward if you have cancer. But there is no point giving people treatments that won’t work. It just causes unnecessary side effects, and there might be another treatment that would work better.
Many of these new medicines are expensive. So giving them to people who are most likely to benefit makes them more cost effective. This also makes them more likely to be approved by the National Institute for Health and Care Excellence (NICE) or the Scottish Medicines Consortium (SMC). Then these treatments can become available on the NHS.
Testing and treatments
Doctors need to do very specific tests on cancers to find out which changes there are inside cancer cells. This is a new and developing area. At the moment only a few of these tests are available for a small number of cell changes in certain types of cancer. The tests are so specialised that they might not yet be available in all cancer centres.
Some drugs are already linked to available tests.
Chronic myeloid leukaemia
A gene change called bcr/abl is found in most chronic myeloid leukaemias. There is now a test for this. If your leukaemia cells test positive, you are likely to respond to a drug called imatinib (Glivec).
A gene change in some lung cancers encourages the cancer cells to grow uncontrollably. This is called the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation. Doctors can test for it. If your cancer cells test positive the cancer may respond to a drug called gefitinib (Iressa).
Some bowel cancers have an altered gene called K-ras. A drug called cetuximab (Erbitux) only works on cancers that have the normal version of this gene, which we can now test for.
Melanoma skin cancer
Some melanoma skin cancers have a changed gene called BRAF V600. Drugs called vemurafenib (Zelboraf) and ipilimumab (Yervoy) work on melanoma that has this gene change.
Is stratified medicine available for me?
Stratified medicine is at an early stage of development and we are learning more about it every day. Some people are already benefiting from this work. Whether it is suitable for you depends on whether:
- scientists have identified gene changes for your type of cancer
- there is a test available for that gene change
- there is a treatment that targets the particular gene change
You can find out about the research and tests available for your type of cancer in the relevant cancer type section.
You can also search our clinical trials database to find information on current clinical trials.
We also need to build a network of labs that can do the gene tests. Cancer Research UK is working with the NHS and pharmaceutical and medical companies to develop more new tests and make them available in the NHS.
This takes time. We have to make sure any new test is sensitive at picking up any changes, and is accurate and reliable. It will be some time before everyone with cancer will be able to have treatment based on the genetic make up of their cancer.
Does stratified medicine always work?
Unfortunately, we can’t guarantee that any treatment will always be successful. Even when you've had the right tests and your cancer has a particular gene change, a targeted treatment doesn’t always work.
We think this is because there are many very complicated signalling pathways in cells. So a treatment might not work because there are other changes in the cell we don’t know about, or don’t have a test for yet. Particular combinations of cell changes may interact. For example, we might block one signal that tells cancer cells to grow. But another signalling pathway might then be triggered, so the cells grow anyway.
We will find out more about which treatments work with each of these cell changes as we continue with this area of research. Most importantly, people will get the treatment they need because we will have a national system in place for carrying out the tests.