Our scientists identify the people with breast cancer who could be treated using glaucoma drugs

Professor Victoria Sanz Moreno and her team, based at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, found these weaknesses in breast cancer, melanoma and acute myeloid leukaemia.

In the future, these findings could pave the way for clinical trials, so the right people are matched to the right treatment.

When breast cancer spreads to other parts of the body, this is called metastatic breast cancer. And whilst it can be treated, it can’t yet be cured.

But to spread, cancer cells first need to move. Tissues in the body can be tightly packed, so to get around this, some cancer cells change shape.

One thing that helps them do this is a molecule called ROCK. It acts a bit like a drawstring inside the cell, keeping the scaffolding of cells tense and making the cells contract and become round. In cancer cells, this generates force for the cells to squeeze through tissue.

In the eyes, the network of cells through which fluid drains is a mesh also controlled by ROCK – when the mesh is too tense and tightly packed, fluid builds up and causes pressure. Drugs called ROCK inhibitors relax this mesh and enable fluid to drain.

But until now, researchers haven’t been able to make ROCK inhibitors work for cancer. This is in part because of the drugs’ side effects, and because we haven’t been able to identify who’s likely to respond well.

The scientists looked at a large database of cancer cells. The database showed how hundreds of cancer cell samples responded to different drugs. And the team used this to look for patterns in the cells that responded well to ROCK inhibitors.

Then they tested what they found in the lab, in tumour samples from patients and in studies in mice.

In breast cancer and other solid tumours, cells were more likely to respond to ROCK inhibitors when they had had a particular gene that was not working as it should, called E-Cadherin.

In non-epithelial solid tumours – such as melanoma – the database showed that cells that respond to ROCK inhibitors tend to have a more rounded shape. They also had high activity in a pathway that drives tumour growth, spread and inflammation, called NFKB.

The team then tested whether similar markers would apply to blood cancers. In the database, acute myeloid leukaemia (AML) cells that responded well to ROCK had a specific set of gene changes.

In all tumour types, cancer cells that responded better to ROCK inhibitors were always the ones with more genes that regulate the cell’s identity and how it divides.

The researchers hope that, in the future, identifying these clues in a biopsy of someone’s cancer could be used to indicate that ROCK inhibitors might work well.  

More work is needed before we know whether these drugs could help people with breast cancer. But the team hope that since these drug are already used to treat glaucoma, clinical trials could start soon.

This study was published in iScience. It was funded by The Institute of Cancer Research, Barts Cancer Charity, Cancer Research UK, Worldwide Cancer Research and UK Research and Innovation and from us at Breast Cancer Now.

We’d also like to extend our heartfelt thanks to our supporters – including Omaze, flagship funders of the research centre - for making this possible.