Lung Cancer is one of the major causes behind death of many patients all around the world. Continuous research work and studies are being carried on to help patients in successful recovery from this disease. The researchers at Weill Cornell Medicine have developed a mouse model that illuminates historical transformation. Lung cancer sometimes respond to initially effective treatments by transforming into a more aggressive small cell lung cancer which then spreads rapidly and has few treatment options.
According to the results published in Science, the researchers have discovered that during transition from lung adenocarcinoma to small cell lung cancer, the mutated cells undergo a change in cell identity via an intermediate, stem cell-like state. These findings worked on understanding how mutated genes can trigger cancer evolution and they suggested targets for more effective treatments.
Study lead Dr. Eric Gardner said, “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.” It took several years to develop and characterize it.
The researchers engineered mice to develop a common form of lung adenocarcinoma, in which epithelial cells are driven by a mutated version of EGFR gene. Then, they turned adenocarcinoma tumors into SCLC-type tumors by shutting off EGFR in the presence of other changes such as losses of the tumor suppressor genes and turning of production of SCLC driver. This study showed that the oncogenes act in a context-dependent manner. The team also discovered that a stem cell-like intermediate was neither adenocarcinoma nor SCLC. The study further supports efforts seeking Therapeutics that target Myc proteins which are implicated in various types of cancers.
The researchers now plan to use their new mouse model to further explore the adenocarcinoma-SCLC transition.
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