Researchers have identified and killed breast cancer cells that evade standard treatments in a study in mice.
They hope it is a step towards the development of new treatments that could prevent relapse in patients.
The scientists, from Professor Greg Hannon’s IMAXT lab at the Cancer Research UK Cambridge Institute at the University of Cambridge, developed the technique to identifying the different types of cells in a tumour.
Using mouse tumours for their study, the method allows them to track cells during treatment to see which types of cell die and which survive.
The progress follows the award of £20million to the IMAXT team under the Cancer Grand Challenges scheme, funded by Cancer Research UK.
Dr Kirsty Sawicka from the Cancer Research UK Cambridge Institute said: “Tumours are incredibly complex, made up of many different types of tumour cells that have acquired genetic mutations as they evolve and replicate – and some of these cells are able to evade standard cancer treatments.
“Until now, it hasn’t been possible to work out which these cells are and what makes them special, but our technique means that we can now do just that.”
Tumours have both normal cells and many types of cancer cells within them. The diverse range of cancer cells within a single tumour is one reason why standard therapies sometimes fail.
Cancer cells that are susceptible to anti-cancer drugs are killed during treatment, which leads to tumours shrinking, meaning the therapy appears successful.
However, a small number of cancer cells in the tumour may survive and be able to regrow – often persistently – which leads to relapses.
In their study, published in eLife, the team used viruses to tag different types of breast cancer cells with a unique genetic ‘barcode’.
After forming tumours from these cells in mice, they treated them with the same drugs used to treat patients with breast cancer.
They scanning the barcodes using recently developed single cell sequencing technologies that look for genes that are turned on or off in a cell.
This enabled them to identify different types of cancer cells, how many of them there were and their characteristics. And they were able to discern which types of cancer cells are not killed effectively by standard treatments.
They discovered that cells that evade chemotherapy are those that have a greater reliance on asparagine. This is an amino acid that cells use to protect themselves from damage.
They administered L-asparaginase, a drug that breaks down asparagine which is used to treat patients with acute lymphoblastic leukaemia. This enable them to target and kill those tumour cells specifically.
Dr Ian Cannell, from the Cancer Research UK Cambridge Institute, said: “Offering some kind of ‘combination therapy’ that adds asparaginase to the standard treatment could be a way of further shrinking tumours in breast cancer patients and reducing their risk of relapse.
“Although we see evidence that these evasive tumour cells are increased in patients after chemotherapy, so far, we’ve only shown that we can target them in mice, so there’s still a long way to go before it leads to a treatment for patients.
“Before we can do that we need to find the best way of administering the drugs – would we give the drugs together, for example, or offer the standard treatment and then asparaginase?”
David Scott, director of Cancer Grand Challenges at Cancer Research UK, said: “Incredible innovations like these are exactly why Cancer Grand Challenges was created. Ambitious ideas from world class scientists – like tracking how individual cells respond to cancer treatments – are what will give us the much needed insights to bring us the more effective cancer treatments of tomorrow and make real differences to patients.”
