Breast cancer can become resistant to treatment by co-opting a gene-silencing mechanism, reports a team led by Steffi Oesterreich at the University of Pittsburgh in Pennsylvania.
The hormone oestrogen, which drives many breast cancers, dampens the activity of the tumour-fighting gene HOXC10, and drugs called aromatase inhibitors free the gene from this repression. But in a genome-wide screen of human breast-cancer cells, the team found that these drugs can also lead to a type of epigenetic modification called methylation — the addition of methyl groups to DNA without changing its sequence — across the genome. This ultimately silences HOXC10, rendering breast-cancer cells resistant to aromatase inhibitors.
Blocking the methylation activity associated with aromatase-inhibitor treatment might delay or prevent resistance to therapy, the authors say.