Lineage-specific intolerance to oncogenic drivers restricts histological transformation. (https://pubmed.ncbi.nlm.nih.gov/38330136/)

These scientists wanted to understand how a type of lung cancer called lung adenocarcinoma (LUAD) can change into another type of lung cancer called small cell lung cancer (SCLC) after treatment with targeted therapies. They were curious about what happens inside the lung cells during this transformation.

To investigate this, the scientists created models in the lab to mimic the transformation of LUAD into SCLC. They discovered that the change from LUAD to SCLC is blocked by a specific protein called Myc. This protein is important for a type of lung cell called pulmonary neuroendocrine cell, which is involved in the development of SCLC.

The scientists also found that when the transformation occurs, another pathway called the Akt pathway becomes activated. By manipulating this pathway, they were able to make the lung cells tolerate the presence of the Myc protein, which is normally not tolerated. This led to the creation of rare cells that are similar to stem cells and resemble a different type of lung cell called pulmonary basal lineage.

These findings suggest that for the transformation from LUAD to SCLC to happen, the lung cells need to have the ability to change and adapt, similar to how stem cells can transform into different types of cells. This research helps us understand more about how lung cancers can change and may lead to new ways to treat these types of cancers in the future.

Gardner EE., Earlie EM., Li K., Thomas J., Hubisz MJ., Stein BD., Zhang C., Cantley LC., Laughney AM., Varmus H. Lineage-specific intolerance to oncogenic drivers restricts histological transformation. Science. 2024 Feb 9;383(6683):eadj1415. doi: 10.1126/science.adj1415. Epub 2024 Feb 9.