Australian researchers have found a gene that drives the most aggressive of breast cancers, and are hoping to find a way to ‘switch it off’.
Researchers found that so-called ‘triple-negative breast cancers’ are two distinct diseases that likely originate from different cell types.
The aggressive form of triple-negative breast cancer appears to arise from stem cells, while the more benign form appears to arise from specialised cells.
Previous studies have shown that breast stem cells are needed for breast growth and development during puberty and pregnancy, although how they evolve from stem cells into specialist cells has been unclear.
The new study has shown that a gene known as ‘inhibitor of differentiation 4’ (ID4) determines whether a stem cell remains a stem cell, or whether it differentiates into a specialist cell.
When the high levels of ID4 in a stem cell are ‘switched off’, other genes that drive cell specialisation are ‘switched on’.
The study by Drs Alex Swarbrick and Simon Junankar from Sydney’s Garvan Institute of Medical Research found that ID4 not only ‘marks’, but appears to control, the highly aggressive form of triple negative breast cancer.
“We found that ID4 is produced at high levels in roughly half of all triple negative breast cancers, and that these cancers have a particularly poor prognosis,” said Swarbrick.
“We also showed that if you block the ID4 gene in experimental models of triple negative breast cancer, the tumour cells stop dividing,” Swarbrick said.
Blocking ID4 switches on the oestrogen receptor3 and several other genes expressed by the best-prognosis breast cancer.
“Oestrogen receptor-positive breast cancers have a relatively good prognosis because the drug Tamoxifen is very effective at blocking the oestrogen receptor and hence their growth,” said Swarbrick.
“We speculate, therefore, that by blocking ID4 it might be possible to turn stem-cell-like breast cancers into less aggressive breast cancers that may even respond to tamoxifen,” he said.
The next step for Swarbrick and his team will be to study the biochemistry of ID4 in a cell – to determine how best to block it in people.
The study is published in the journal Nature Communications.