A preclinical study conducted by Peter Mac researchers has provided new insights into what causes cancer of the oesophagus to develop at the genetic level.
They found that a gene called SMAD4 acts like a brake to stop a tumour developing in a pre-cancerous condition called Barrett’s oesophagus.
Barrett’s oesophagus occurs when chronic stomach acid reflux — which some people experience as heartburn — damages the normal lining of the oesophagus, which is then replaced by an abnormal lining.
People with Barrett’s oesophagus develop gene mutations in the cells of this abnormal lining, but each year only about one in 400 cases progress to cancer.
It’s not known which gene mutations cause it to progress, and therefore it’s hard to predict who is at risk.
This study in mice, found that when this SMAD4 gene is mutated it stops working as a cancer brake, leading to further mutations in other genes that contribute to cancer development, and the formation of a tumour.
“This mutation of the SMAD4 gene is responsible for about one in seven cases of oesophageal cancer,” says Dr Jovana Gotovac, who was the first author on the study published in Cellular and Molecular Gastroenterology and Hepatology this week.
“This research is important because oesophageal cancer rates are increasing and most patients can’t be cured with our current treatments,” says Associate Professor Nick Clemons, senior author on the study and head of the Tumourigenesis and Cancer Therapeutics Laboratory.
“Therefore, we want to understand how different gene mutations in Barrett’s oesophagus contribute to cancer development so we can develop new treatments, but also so we can predict who is at risk of developing oesophageal cancer.”
This will allow patients to start being treated earlier when curing their cancer is more achievable with the currently available therapies.
“We can monitor patients with Barrett’s oesophagus for the presence of a SMAD4 mutation, which would indicate the presence of early cancerous cells,” says Dr Gotovac who undertook the work as part of her PhD research.
“Then they could receive a treatment that burns away the abnormal cells, thus avoiding the treatments required for advanced cancers — which also don’t work in most patients.”
“We’re now trying to understand how the normal version of the SMAD4 gene works to stop cancer development,” says Associate Professor Clemons.
“We hope this will lead to us identifying new ways to treat patients who have progressed to oesophageal cancer.”
“We are very excited about this important discovery made by Nick and his team,” says Executive Director Cancer Research Professor Ricky Johnstone.
“Understanding the genetic basis of oesophageal cancer is very important if we are to develop new therapies and provide treatment options for our patients.”