The active substance dexamethasone is a synthetic signalling substance with a similar effect to the body’s own stress hormone cortisol.

A research group at the University of Basel has found evidence that this drug, which has been in use for a long time, could have a new, additional effect in certain treatment-resistant breast cancers.

Breast cancer of the “oestrogen receptor-positive” (ER+ for short) subtype can usually be treated with anti-hormonal therapy.

The target of this therapy is the oestrogen receptor, which is hyperactive in these tumours and drives abnormal cell division.

Hormone therapy uses drugs that deactivate or break down the oestrogen receptor, thereby slowing the growth of cancer cells.

However, this type of tumour sometimes forms metastases that no longer respond to hormone therapy.

Fewer metastases

A research team led by Professor Mohamed Bentires-Alj from the Department of Biomedicine at the University of Basel and the University Hospital Basel reports in the journal EMBO Molecular Medicine that dexamethasone can combat precisely these therapy-resistant metastases.

In trials with mice with therapy-resistant ER+ tumours, dexamethasone reduced liver metastases and prolonged the animals’ survival.

Further analyses provided more detailed insights into how the drug achieves this effect: dexamethasone activates the glucocorticoid receptor.

This, in turn, suppresses the production of the oestrogen receptor.

“As a result, the cancer cells lose the main driver of tumour growth,” explains Dr Madhuri Manivannan, lead author of the study.

In addition to the trials with mice, the researchers also used patient-derived tumour tissue grown in the laboratory known as organoids.

Here, they also observed that the amount of oestrogen receptor decreased with the addition of dexamethasone.

New benefits for proven medication

“Dexamethasone could potentially directly support certain breast cancer therapies, not just as a concomitant treatment for nausea and inflammation,” says Dr Charly Jehanno, who led the research project.

“However, these results, particularly the loss of oestrogen receptor, need now to be confirmed directly in patients with breast cancer”.

If the metastasis-inhibiting effect proves to be true, this long-established drug could potentially be repurposed.

However, the researchers stress that dexamethasone would not be suitable for all breast cancer patients.

“Dexamethasone is an example of how the same drug can have very different effects on the course of the disease in different forms of breast cancer,” says Professor Mohamed Bentires-Alj.

In 2019, his team reported in the journal Nature that dexamethasone actually promotes metastases in another type of breast cancer (triple-negative).

Source: University of Basel