A new approach could pave the way for new treatments to prevent relapse in breast cancer patients

Cambridge scientists have managed to identify and kill those breast cancer cells that escape standard treatments in a study on mice. The approach is a step towards developing new treatments to prevent relapses in patients.

Tumors are complex entities made up of many types of cells, including cancer cells and normal cells. But even within a single tumor there is a huge array of cancer cells, and that’s one reason why standard therapies fail.

When a tumor is treated with anticancer drugs, the drug-sensitive cancer cells die, the tumor shrinks, and the therapy appears to be successful. But in reality, a small number of cancer cells in the tumor may be able to survive treatment and grow back, often more persistently, causing a relapse.

In a study published in and LifeScientists from Professor Greg Hannon’s IMAXT laboratory at the University of Cambridge’s Cancer Research UK Cambridge Institute have developed a new technique for identifying the different cell types in a tumour. Their method, developed in mouse tumors, allows them to track cells during treatment, seeing which cell types die and which survive.

The IMAXT team had previously received £20 million from Cancer Grand Challenges, funded by Cancer Research UK.

Tumors are incredibly complex, made up of many different types of cancer cells that have acquired genetic mutations as they evolve and replicate – and some of these cells are capable of evading standard cancer treatments. Until now, it hasn’t been possible to figure out what these cells are and what makes them special, but our technique means we can now do just that.”


Dr Kirsty Sawicka, Cancer Research UK Cambridge Institute

The team used viruses to tag different types of breast cancer cells with a unique genetic ‘barcode’. They then formed tumors from these cells in mice and treated them with the same drugs used to treat breast cancer patients.

By scanning barcodes using recently developed single-cell sequencing technologies — which look for those genes that are turned on or off in the cell — they were able to identify the different types of cancer cells, how many of these cells are there and what their characteristics are – and what types of cancer cells are not killed effectively by standard treatments.

The team noted that the cells that escape chemotherapy are the ones that are most dependent on asparagine, an amino acid that cells use to protect themselves from damage. Then by administering L-asparaginase — a drug currently used to treat patients with acute lymphoblastic leukemia, which breaks down asparagine — they were able to specifically target and kill these cancer cells.

Dr Ian Cannell of Cancer Research UK Cambridge Institute said: ‘Offering some sort of ‘combination therapy’ adding asparaginase to standard treatment could be a way to further shrink tumors in breast cancer patients and reduce the risk of recurrence.

“Although we see evidence that these evasive cancer cells are increased in patients after chemotherapy, so far we have shown that we can only target them in mice, so there is still a long way to go before it leads to a treatment for patients. Before we can do, we have to find the best way to deliver the drugs, for example, give the drugs together or offer the standard treatment and then asparaginase.”

David Scott, Director of Cancer Grand Challenges, Cancer Research UK, said: “Incredible innovations like these are exactly why Cancer Grand Challenges was created. really make a difference to patients.”

Source:

Magazine reference:

Wild, SA, et al. (2022) Clonal transcriptomics identifies mechanisms of chemoresistance and allows rational design of combination therapies. and Life. doi.org/10.7554/eLife.80981.

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