‘Water Pill’ Prevents Lung Cancer Drug Resistance

A cheap diuretic could extend the effectiveness of existing lung cancer drugs, research suggests.

AsianScientist (Oct. 5, 2016) – Combining lung cancer drugs with a commonly used blood pressure drug called ethacrynic acid could make treatment more effective, suggests a new study published in Cell Discovery. The early-stage research, conducted on human cells in the lab and on mice, was led by scientists from Fudan University in China and Imperial College London.

Almost two million people are diagnosed with lung cancer every year worldwide and it is the top international cancer killer. The drug erlotinib is prescribed to between 10 to 30 percent of patients with non-small cell lung cancer, which accounts for 85 percent of all lung cancer cases. Erlotinib exploits a mutation of the epidermal growth factor receptor in these patients, blocking the receptor and preventing tumor growth.

Unfortunately, the cancer cells become resistant to erlotinib by developing a second mutation in about half the cases. Although alternative drugs are available once erlotinib stops working, these are much more expensive–and they can also stop working due to cancer cells developing resistance. But until now scientists only partially understood how this second mutation allowed the cancer cells to protect themselves against erlotinib.

In the current study, the team showed that the resistance could be reversed using ethacrynic acid, a simple and cheap diuretic or ‘water pill’ that is used to treat swelling, fluid retention and high blood pressure.

The team found that if they raised glutathione levels in cancer cells in the lab, they reversed resistance to the drug erlotinib, and the treatment was once again able to kill cancer cells. They found that ethacrynic acid raised glutathione levels by triggering the kidneys to remove more water from the body and also blocking the breakdown of glutathione.

Professor Michael Seckl, lead author from the Department of Surgery and Cancer at Imperial said, “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. This could potentially provide patients with more treatment options and save money in financially challenged health services.”

The team are now considering the possibility of translating their findings to human trials within the next three years and are currently seeking funding, said Seckl.

The article can be found at: Li et al. (2016) Decreased Glutathione Biosynthesis Contributes to EGFR T790M-driven 2 Erlotinib Resistance in Non-small Cell Lung Cancer.


Source: Imperial College London; Photo: Pixabay.
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