Lung cancer treatment boosted by simple blood pressure drug
A common blood pressure drug may make a type of lung cancer treatment more effective, suggests a new study partly funded by Worldwide Cancer Research and published this week in the journal Cell Discovery.
Worldwide Cancer Research scientist and lead author Professor Michael Seckl 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 lung cancer drug erlotinib. This could potentially provide patients with more treatment options and save money in financially challenged health services.”
Almost 2 million people are diagnosed with lung cancer every year worldwide and it is the biggest global cancer killer. There are two types, the rarer small cell lung cancer and the more common non-small cell lung cancer. The drug erlotinib is prescribed to between 10 - 30 per cent of patients with non-small cell lung cancer who carry a particular genetic mutation on their cancer cells. Erlotinib blocks this mutation and halts cell growth. However, the cancer cells quickly evolve resistance to the drug’s deadly effects and within a matter of months patients no longer benefit from the drug.
Although alternative drugs are available once erlotinib stops working, these are much more expensive – and they can also stop working, again due to cancer cells developing resistance.
Previous studies have found that, in at least half of cases, the cancer cells become resistant to erlotinib by developing a second mutation. But scientists only partially understood how this additional mutation protected the cancer cells from dying.
In this study, the team found the second mutation lowers levels of a naturally-occurring antioxidant called glutathione. If glutathione levels were raised in cancer cells in the lab, it reversed resistance to the drug erlotinib, and the treatment was once again able to kill cancer cells. Spurred on by their finding, the team then looked for medicines that raise glutathione levels.
They found the ‘water pill’ ethacrynic acid, a diuretic used for 30 years to treat swelling, fluid retention and high blood pressure, raised glutathione levels. Studies in mice confirmed that using the diuretic alongside the cancer drug erlotinib reversed resistance to the drug, and enabled it to kill lung cancer cells.
“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 want to start patient trials within the next three years” explained Professor Seckl.
The research was supported by the European Commission, Cancer Research UK, Worldwide Cancer Research, Cancer Treatment and Research Trust and the NIHR Imperial Biomedical Research Centre.
- Full bibliographic informationDecreased glutathione biosynthesis contributes to EGFR T790M-driven 2 erlotinib resistance in non-small cell lung cancerHongde Li, William Stokes, Emily Chater, Rajat Roy, Elza de Bruin, Yili Hu, Zhigang Liu, Egbert F. Smit, Guus J.J.E. Heynen, Julian Downward, Michael J. Seckl, Yulan Wang, Huiru Tang, Olivier E. PardoCell Discovery, 26 September 2016
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