Study shows increase in IL-6 secretion can reduce Tarceva sensitivity to treat lung tumor cells

February 12, 2016

This subpopulation of tumor cells were observed to secrete elevated amounts of TGF-??, a type of growth factor that plays a role in cell differentiation, development, and in regulation of the immune system. Up-regulation of TGF-?? in these tumor cells resulted in increased secretion of a signaling molecule called IL-6, which among other things is also involved in immune responses. This subset of tumor cells with up-regulated TGF-?? and increased IL-6 secretion was observed to resist treatment with Tarceva, independently of the EGFR pathway.

"This led us to the idea that inflammation might be one of the factors that could reduce a lung tumor cell's sensitivity to Tarceva," Sordella says. Since IL-6 and TGF-?? are actively produced during the general inflammatory process, the team was led to explore whether inflammation mediated by non-cancer cells in the tumor microenvironment might also play a role in resistance to Tarceva. Using mouse models, the team was able to show precisely that.

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

Source: Cold Spring Harbor Laboratory