Lung tumours called adenocarcinomas sometimes respond to initially effective treatments by transforming into a much more aggressive small cell lung cancer (SCLC) that spreads rapidly and has few options for treatment.
Researchers at Weill Cornell University developed a mouse model that illuminates this problematic process, known as histological transformation.
The findings, published in the journal Science, advance the understanding of how mutated genes can trigger cancer evolution and suggest targets for more effective treatments.
The researchers discovered that during the transition from lung adenocarcinoma to SCLC, the mutated cells appeared to undergo a change in cell identity through an intermediate, stem cell-like state, which facilitated the transformation.
“It is very difficult to study this process in human patients. So my aim was to uncover the mechanism underlying the transformation of lung adenocarcinoma to small cell lung cancer in a mouse model,” said lead author Dr. Eric Gardner, a postdoctoral fellow at Weill Cornell Medicine.
SCLC most commonly occurs in heavy smokers, but this type of tumour also develops in a significant number of patients with lung adenocarcinomas, particularly after treatment with therapies that target a protein called Epidermal Growth Factor Receptor (EGFR), which promotes tumour growth.
“It is well known that cancer cells continue to evolve, especially to escape the pressure of effective treatments,” said Dr. Harold Varmus, Professor at the varsity.
“This study shows how new technologies — including the detection of molecular features of single cancer cells, combined with computer-based analysis of the data — can portray dramatic, complex events in the evolution of lethal cancers, exposing new targets for therapeutic attack,” he said.
IANS