Researchers discover key to drug resistance in common breast cancer treatment

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI), the University of California (UC), San Diego and the University of Illinois 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 tumor 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 online ahead of print 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.

“Cytokines change the shape of the estrogen receptor, and that change overrides the inhibitory effects of tamoxifen and leads to drug resistance,” said TSRI Associate Professor Kendall Nettles, who led the new study alongside senior author Christopher K. Glass and study first author Joshua D. Stender of UC San Diego. “These findings dramatically alter our understanding of the biological actions of pro-inflammatory cytokines in breast cancer cells.”

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