Researchers from the Institute of Cancer Research (ICR) have revealed how breast cancer cells can become dormant and have suggested a strategy to target them to prevent relapse in patients.
Funded by Cancer Research UK (CRUK) and published in the journal Cancer Discovery, the study explores the role of epigenetics – how the body reads DNA without changing the DNA code itself – in controlling dormant cancer cells.
Responsible for 80% of all breast cancers, oestrogen receptor (ER)-positive breast cancer patients have a continued risk of recurring cancer, even after diagnosis and surgery, and for some, years of hormone therapy will be required.
After discovering in the Breast Cancer Now Toby Robins Research Centre that cancer cells could be prevented from becoming dormant by inhibiting enzymes that catalyse regulators, ICR researchers studied ER-positive breast cancer cells tagged with unique barcodes.
The team mimicked hormone therapy treatments on the cells and discovered that some cells became dormant and avoided treatment.
Using mass spectrometry, researchers found that hormone therapy treatment could trigger changes to histone modifications – an epigenetic modification where chemical tags are added to/removed from DNA or proteins DNA is wrapped around – including H3K9me2 as the cells went into “hibernation”.
Researchers then inhibited the enzyme G9a, which catalyses H3K9me2, on cells treated with hormone therapy and discovered that it prevented the cancer cells from entering dormancy, ultimately eliminating the cells.
After testing it on cells that were already in a dormant state, researchers revealed that this process successfully eliminated dormant cancer cells.
Additionally, researchers found that patients with ER-positive breast cancer who had a low expression of enzymes, including G9a, had a significantly lower risk of relapse for up to 20 years.
Professor Luca Magnani, professor of epigenetic plasticity, ICR, hopes that the findings “lead to research to target… dormant breast cancer cells so that one day… patients can be sure that their cancer will not return,” without requiring hormone therapy.
In February, ICR researchers revealed how some advanced ER-positive breast cancers become resistant to widely used hormone therapy, fulvestrant, using blood samples from the plasmaMATCH clinical trial to analyse traces of cancer DNA in the blood.