Using a low dose of the epigenetic therapy drug decitabine, which is currently used to treat some blood cancers, the researchers significantly suppressed the growth of endocrine-resistant breast tumours in mice and increased survival time by 90%. The finding, which will be tested in a future Phase I clinical trial, is a potential gamechanger for the more than 4,000 people who are diagnosed with endocrine-resistant breast cancer each year in Australia alone.
Epigenetic change drives breast cancer treatment resistance
An estimated 70% of all diagnosed breast cancers are oestrogen receptor positive (ER+), which means their growth is activated by oestrogen — a hormone that plays a key role in sexual and reproductive health in women.
While endocrine therapy that suppresses oestrogen in the body can slow or stop the growth of these tumours, more than 30% of patients develop resistance, with their tumours no longer requiring oestrogen to grow.
In a 2020 study, the Garvan team investigated the endocrine-resistant cancer’s epigenome, the layer of instructions that organises and regulates DNA’s activity, and revealed that endocrine resistance is linked to methyl groups attaching to regulatory regions of DNA and changing the 3D structure of DNA inside cancer cells.
New approach to breast cancer therapy
“In this current study, we set out to reverse the abnormal methylation patterns and restore the 3D DNA structure in the endocrine-resistant ER+ breast cancers using epigenetic therapy,” says first author Dr Joanna Achinger-Kawecka, Head of the 3D Epigenome in Cancer Group at Garvan.
“We found that decitabine removed methyl groups at specific DNA regulatory regions, rewiring the 3D structure of DNA to not only reactivate the production of oestrogen receptors, but also activate tumour suppressor genes that can reduce cancer growth.”
“After treating patient-derived endocrine resistant breast cancer tumours with decitabine alone, we were surprised to see cancer growth significantly reduced in mice,” says co-first author Associate Professor Clare Stirzaker, Head of the Epigenetic Biomarker Group.
Sources : www.sciencedaily.com