New drug active against most aggressive type of lung cancer

Scientists have shown that a new drug could prove useful in treating small cell lung cancer, the most aggressive form of lung cancer. The research, published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-2270), also helps identify which patients are most likely to respond to the treatment.

One treatment approach currently being investigated by cancer scientists is finding drugs that exploit the change in energy production in tumors. Cancer cells switch to using glycolysis, a process that requires less oxygen and produces lactate as a by-product. Certain molecules known as monocarboxylate transporters (MCTs) are involved in the movement of lactate out of cells. Drugs that target MCTs have been shown to stop tumor growth.

Scientists from the Cancer Research UK Manchester Institute, based at The University of Manchester and part of the Manchester Cancer Research Centre in the United Kingdom, teamed up with experts at AstraZeneca, to test the drug AZD3965 on small cell lung cancer cells. AZD3965 targets one of these molecules, MCT1, in lung cancer cells and in mouse models.

"Small cell lung cancer has a dismal prognosis and we have seen little improvement in treatment for many years. More targeted therapies are needed to help those patients whose tumors become resistant to chemotherapy. This new drug—AZD3965—is currently in clinical trials, but it has not yet been tested in small cell lung cancer," said lead researcher Professor Caroline Dive, PhD, of the University of Manchester.

The team investigated the sensitivity of small cell lung cancer cells to AZD3965 and showed that the drug had an effect in those cells that lacked an alternate lactate transporter, MCT4. The effect was to increase the level of lactate in cells and, more importantly, reduce tumor growth.

The researchers then looked at tumor samples taken from lung cancer patients and found that high levels of MCT1 were linked to worse patient prognosis.

"We propose that this drug will be most useful in this subset of patients who have elevated MCT1 levels and need more effective treatments,” added Dive. "Our laboratory results are promising and certainly provide encouragement to test this treatment clinically in patients with small cell lung cancer."

"Lung cancer is still the leading cancer killer, and we are working on a number of potential treatment options that could provide patients with a better chance of beating the disease. Targeting tumor cell metabolism represents a novel and exciting approach, and we are delighted to be working with The University of Manchester and Cancer Research UK to investigate the utility of AZD3965 as a potential novel cancer treatment," said Susan Galbraith, MB, MChir, PhD, and head of the oncology innovative medicines unit at AstraZeneca.

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