A blood pressure-lowering drug called Edecrin (ethacrynic acid) may be used to prevent resistance to the lung cancer agent Tarceva (erlotinib), scientists from Imperial College London and Fudan University in China found.
Findings from the early-stage research study, “Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer,” were published in Cell Discovery.
“Although these are very early-stage results, and are yet to be applied to patients in trials, they suggest the addition of a very cheap diuretic may extend the amount of time we can use the cancer drug erlotinib,” Michael Seckl, PhD and lead author from the Department of Surgery and Cancer at Imperial, said in a news release. “This could potentially provide patients with more treatment options and save money in financially challenged health services.”
Lung cancer is the main cancer killer and non-small cell lung cancer (NSCLC) represents approximately 85% of such cases. Among patients with NSCLC, about 10% to 30% have a mutation in the epidermal growth factor receptor (EGFR) that can be targeted effectively with Tarceva or Iressa (gefitinib).
Unfortunately, most patients acquire resistance to these drugs quickly, limiting the benefits to patients’ survival. Previous research had shown that tumor cells became resistant to Tarceva by acquiring a second mutation in EGFR, but researchers did not fully understood how this mutation was protecting cancer cells from Tarceva.
In the new study, the research team gained further insights into how this second mutation allowed the cancer cells to protect themselves against Tarceva.
The study suggests this second mutation decreases levels of glutathione, a naturally occurring antioxidant. However, by increasing the levels of glutathione in cancer cells cultured in the lab, researchers were able to reverse resistance to Tarceva.
Encouraged by their discovery, researchers proceeded to test other drugs that increased the levels of glutathione. They found that Edecrin, which is commonly used to treat high blood pressure or fluid retention, was able to increase the levels of glutathione.
To validate their findings, researchers tested the combination of Tarceva and Edecrin in mice, and were able to confirm that Edecin reversed resistance to Tarceva, and enabled it to kill lung cancer cells. The team will work now to translate these findings to human trials.
“We urgently need new treatments for lung cancer patients, and this research suggests we can boost the effectiveness of an existing drug, rather than switch to another new expensive treatment. We are now seeking funding to enable patient trials within the next three years,” said Seckl.