Research uncovers how to target dormant breast cancer cells

Cancer cells

Scientists have discovered how breast cancer cells can ‘hibernate’ to avoid treatment and ‘wake up’ years later – causing a relapse that is more difficult to treat.

Their research, published in the journal Cancer Discovery, reveals the role of epigenetics in controlling how cancer cells can become dormant – and suggests a strategy to target it before the cells wake up.

Patients with oestrogen receptor positive (ER+) breast cancer (80% of all breast cancers) have a continued risk of their cancer recurring for many years or even decades after their original diagnosis and surgery. To reduce their risk of relapse, patients undergo five to ten years of hormone therapy to target any remaining cancer cells.

Professor Luca Magnani, Professor of Epigenetic Plasticity at The Institute of Cancer Research, London, said: “Our research identified a key mechanism used by cancer cells to evade therapy by remaining in a dormant state, hibernating before they ‘wake up’ years later and begin to rapidly divide again. I hope our early findings will next lead to research to target these dormant breast cancer cells so that one day, without the need for years of hormone therapy, patients can be sure that their cancer will not return.”

Epigenetic changes

The team at The Institute of Cancer Research, London, found that this hormone therapy could in some cases play a role in triggering epigenetic changes that alter the state of some breast cancer cells, causing them to become dormant and evade treatment.

They discovered that specific changes in key epigenetic regulators that control gene transcription, including the modification of histone H3 at lysine 9 (H3K9me2), were responsible for this dormant state.

The scientists found that blocking these regulators – by inhibiting the enzymes that catalyse them – prevented the cells from becoming dormant, and killed the cancer cells that were already dormant. They also found that in people with low expression of these enzymes, their cancer had a lower risk of coming back years later.

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, and a leading researcher of epigenetics and cancer, said: “This research adds to the growing body of evidence for the role of epigenetic regulation in cancer’s complex behaviour. We know that cancer will adapt and evolve to evade treatment, and this study shows how it will lie dormant to hide from treatment. Drugs targeting epigenetic modifications are already in development, and I hope that this research will pave the way to new treatments that prevent breast cancer from returning.”

Diana Spencer, Senior Digital Content Editor, DDW

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