A new study in collaboration with the Laboratory of the University of Kentucky Markeyskogo Cancer Center shows that in some cases, one genetic subtype of non-small cell lung cancer is transformed into another.
This switching type lung cancer is associated with resistance to therapy and the present study focuses on its mechanism. The work was conducted in collaboration with laboratories in Kentucky, New York and Boston.
Previously, scientists have been unclear which cells in the adult lung may be "derived cells" of the two major subtypes of non-small cell cancer, adenocarcinomaand squamous cell carcinoma. In addition, the researchers wondered what the differences in the organization of the DNA is determined by two subtypes of lung cancer. Adenoskvamoznaya lung tumor, clinically defined by the presence of adenocarcinoma and squamous lesions within the same tumor, it is assumed that adenocarcinoma and squamous cell cancer could come from the same cells in the lungs, but the evidence for this theory is not enough.
Published in Nature Communications study showed that adenocarcinoma cells change to squamous due to reorganization of the DNA in a particular way. Starting with a mouse model of lung cancer, scientists have confirmed genetics, comparing it to the human lung tumor adenoskamoznoy - genetics identical, including the activation of an oncogene KRAS. Next, the research team used tests transplant, to demonstrate that installed adenocarcinoma tumors can skip to the squamous cell carcinoma of the lung in mice.
Then the group identified various lung cells and showed that only certain cell may cause lung tumors capable of undergoing transformation.
"These are of interest because show which cells in the lungs cause adenoskvamoznye tumor - said study co-author Christine Fillmore Branson, associate professor of toxicology and biology UK cancer -. And the technique that we have used for the transformation of the isolated cells can be applied to many models of lung cancer. "
Oncologists observed "cancer switch" after failure EGFR tyrosine kinase inhibitor, as clinically warranted hold the second biopsy. However, a second biopsy is usually not carried out after chemotherapy, which, according to Branson, may be reconsidered for the understanding of the exact mechanisms of resistance to therapy.
"Now that we have the opportunity to look at the molecular mechanism of switching types of cancer, we can understand how to control this phenomenon for improving the therapeutic results," - says Branson.