Three-quarters of all breast cancer tumours are driven by the hormone estrogen.
These tumours are frequently treated with drugs to suppress estrogen receptor activity, but unfortunately, at least half of patients do not respond to these treatments, leaving them with drug-resistant tumours and few options.
Now, scientists have found that two immune system molecules may be key to the development of drug resistance in estrogen-driven breast cancers.
The researchers believe this finding may open the door to novel therapeutic approaches and influence treatment decisions for the tens of thousands of patients who suffer from estrogen-driven breast cancers.
These molecules, which are cytokines called interleukin 1 beta (IL1β) and tumour necrosis factor alpha (TNFα), had previously been linked to the spread of drug-resistant cancer.
But scientists were unsure of the exact mechanisms that led these molecules to drive drug resistance.
The new study, published in the journal Molecular Cell, reveals that IL1β and TNFα turn on pathways that modify the actual shape of the estrogen receptor.
This phenomenon appears to drive resistance to the common anti-cancer drug tamoxifen.
Striking Back at Drug Resistance
Using a combination of genomic, cellular, biochemical and structural approaches, the researchers found that the way these cytokines alter the estrogen receptor are sufficient to induce growth of breast cancer cells.
Scientists found that in addition to reversing tamoxifen suppression of growth, cytokine activation of the estrogen receptor also enhanced the invasive properties of a specific line of human breast cancer cells known as MCF-7, the most studied human breast cancer cell in in the world.
Using x-ray crystallography, researchers developed an atomic snapshot of the estrogen receptor to show how these shape changes occur and how the process might be blocked.
They pointed out that both inflammation and immune cells are known causes of resistance, but if that inflammation can be blocked, resistance can be reduced or eliminated.
“These tumours can reprogram the immune cells to their advantage so that the cells become tumour supportive,” they said.
“We think we can produce hormone therapies that can, in essence, re-reprogram the immune system or prevent it from altering the receptor in the first place, which is an obvious strategy for blocking these adverse effects.”
Article was originally published in Knowridge Science Report 24 March 2017.