Researchers have discovered new mechanisms of resistance to targeted lung cancer, according to a study published in Proceedings of the National Academy of Sciences (2010 Aug 31;107(35):15535-40).

To investigate the modes of tumor resistance to targeted therapies, Raffaella Sordella, PhD, an assistant professor at Cold Spring Harbor Laboratory, and her team focused on erlotinib, a small-molecule drug approved by the FDA for patients with difficult-to-treat cancers, including non-small lung cancer (NSCLC) and pancreatic cancer.

Researchers found that the population of NSCLC cells within untreated tumors resistant to erlotinib accounted for about 3% of the tumor samples studied. The team reported that this finding is suggestive of something scientists call EMT: the transition of normal epithelial cells to mesenchymal cells, which are cells with an increased metastatic potential.

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The team continued their study and explored whether inflammation mediated by non-cancer cells in the tumor microenvironment might also play a role in resistance to erlotinib and confirmed their predictions.

“Why IL-6 seems to be required for the survival of the cancer cells is not yet clear,” Dr. Sordella concluded. “We hypothesize that it plays a role in protecting cells from programmed cell-death, or apoptosis. We expect to investigate the possibility in future studies.”