An exciting new study is suggesting that a novel treatment combining two currently available and approved drugs could successfully target nearly 85 percent of current lung cancers. With fewer side effects than traditional chemotherapy, the new treatment is set to move into a phase 2 human clinical trial within 12 months.

Much recent work has been done to reveal the role of epidermal growth factor receptor (EGFR) in lung cancers. New drugs that inhibit EGFR have been developed, and approved for use, to treat non-small cell lung cancers (NSCLCs) but they have frustratingly displayed limited efficacy, often only working 10 to 15 percent of the time.

"There has been a tremendous effort over the past several years to block EGFR as a treatment for lung cancer, but this therapy only works in a small subset of patients," explains Amyn Habib, senior author on the new research. "The cancer fights back with a bypass pathway."

Tracking down and blocking that "bypass pathway" has been fundamental to the new research from Habib and his team. The researchers found that when EGFR is blocked, levels of another protein called tumor necrosis factor (TNF) rise. So it seemed reasonable to explore whether EGFR inhibitors would be more effective in treating lung cancer when paired with TNF inhibitors.

In an animal study the researchers found that non-small cell lung cancers were much more sensitive to EGFR inhibitors when TNF was blocked. In these early experiments the researchers used a drug called thalidomide as the primary TNF inhibitor. While thalidomide certainly has a controversial history, it has recently been undergoing new evaluation as a useful anti-cancer agent.

As both drugs are already approved for human use by the FDA it is hoped a phase 2 human clinical trial of the new dual-drug treatment can be fast-tracked. The proposed clinical trial will not only encompass lung cancer patients but also those with glioblastomas, another cancer known to be associated with EGFR.

"If this strategy is effective, then it might be broadly applicable not only against lung cancer but also against other cancers that express EGFR, which include brain, colon, and head and neck cancers," says David Gerber, an oncologist set to lead the upcoming clinical trial.

Non-small cell lung cancers comprise almost 85 percent of all lung cancers, making this new finding dramatically significant in the field of cancer research. If proven effective in human trials, this new combination of pre-existing drugs would fundamentally alter how lung cancers are treated.

The new research was published in The Journal of Clinical Investigation.

Source: UT Southwestern

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