Why targeted drug doesn’t benefit patients with early-stage lung cancer

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The drug erlotinib is highly effective in treating advanced-stage lung cancer patients whose tumors have a particular gene change, but when the same drug is used for patients with early-stage tumors with the same gene change, they actually fare worse than if they took nothing. A study by researchers at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC — James) and at Cincinnati Children’s Hospital might show why.

Oncologists use erlotinib to treat lung cancers that have a mutation in a gene called epidermal growth factor receptor (EGFR). The gene mutation causes EGFR to run like it has a stuck accelerator, and erlotinib blocks the overactive molecule. The study shows that while erlotinib effectively causes tumors to shrink — suggesting that the drug is helping — this drug also increases the aggressiveness of the tumor so that growth is accelerated when therapy ends. This study finds that this is due to a secondary and previously unknown effect of inhibiting EGFR.

The study’s key technical findings include:

  • In two non-small-cell lung cancer cell lines, erlotinib treatment killed 84 percent and 75 percent of cells; of the surviving cells, 23 percent and 70 percent were stem-like cells, respectively (versus 4 percent and 18 percent of control cells);
  • Erlotinib treatment increased the potential for growth of surviving lung cancer cells;
  • Erlotinib treatment increased the number of stem-like cells through activation of the Notch3 receptor.

Source by : Science Daily News

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