Australian researchers have identified unique molecular characteristics of an aggressive, hard-to-treat type of lung cancer known as adenocarcinoma that could help identify patients most likely to respond to immunotherapies.
The researchers at the Walter and Eliza Hall Institute in Melbourne also identified a possible blood biomarker produced by the deadly disease, raising hope of an early detection test.
Adenocarcinoma accounts for around 40 per cent of lung cancers and is often associated with a history of smoking, but is also the most commonly diagnosed lung cancer in non-smokers.
It occurs more frequently in females and in young people than other types of lung cancer.
“These cancers are very aggressive, are resistant to standard therapies and have a poor prognosis, so new therapies are urgently needed,” Dr Sarah Best from the Walter and Eliza Hall Institute said.
Working with colleagues at Metabolomics Australia, Dr Best and Dr Kate Sutherland focused on the role of two cell signalling pathways – KEAP1/NRF2 and PI3K – which are known to be involved in adenocarcinomas.
The study, published in the journal Cell Metabolism, found more than one in five lung adenocarcinomas had specific alterations in the KEAP1/NRF2 pathway, which provided an environment that allowed the cancer to thrive and grow.
“This is a quite significant proportion of these tumours,” Dr Sutherland said.
Importantly, the researchers showed in mouse models these tumours responded to anti-PD-1 and anti-CTLA-4 immunotherapies.
“When we used these therapies in our pre-clinical models we were able to show that the tumours did regress following treatment,” Dr Sutherland said.
The research also showed these cancers make a “metabolic by-product” that was detected in the blood.
“We believe this offers great hope for being able to provide a simple blood test that could be used to detect these tumours at an early stage but also to possibly detect the patients that may respond to immunotherapy,” Dr Sutherland explained.
The next step is to analyse human samples to prove the same is true in lung adenocarcinoma patients.
Cancer Council Australia CEO, Professor Sanchia Aranda praised the research and said it could “absolutely” be life-saving in the future.
“Lung cancer is the most commonest cause of cancer deaths in Australia for both men and for women, it overtook breast cancer a while ago now, and there are very few effective treatments but particularly no effective early detection tools,” Professor Aranda said.
“A nano-diagnostic or a blood test diagnostic would mark a major advance for high risk individuals.
“Even though it’s early days these are the sorts of studies that will actually get into practice pretty quickly because the treatments are there.”