Statin, Targeted Therapy Combination May Help Combat NSCLC

Investigators at the Icahn School of Medicine at Mount Sinai have been analyzing US Food and Drug Administration (FDA)-approved agents for treating non-small cell lung cancer (NSCLC) and found that by combining the statin fluvastatin (Lescol) and the FDA-approved melanoma drug trametinib (Mekinist), it may be possible to combat NSCLC in an entirely new way.

In a study published in the journal Cell Reports, researchers report that they developed a multigene lung cancer model in Drosophila (fruit fly) to better understand the mechanisms that promote tumors in NSCLC. Using Drosophila and human lung cancer cell lines, they targeted two of the most common genetic mutations associated with NSCLC: Ras and PTEN (P13K).

“We developed Drosophila lung cancer models by targeting Ras alone and in combination with PTEN knockdown in the tracheal system of the fruit fly,” said Ross Cagan, PhD, who is a professor in the Department of Developmental and Regenerative Biology, Senior Associate Dean of the Graduate School of Biomedical Sciences, and Director of the Center for Personalized Cancer Therapeutics at Icahn School of Medicine at Mount Sinai, in a news release. “This led to formation of tumor-like growths.”

Using a robotics-based screening approach, researchers screened a library of 1,192 FDA-approved drugs for any that suppressed tumors in the fly and identified several that improved overall survival. Based on their analyses, they decided to explore combining the MEK inhibitor trametinib and the commonly prescribed cholesterol-lowering drug fluvastatin. Oral administration of these drugs inhibited Ras and the PI3K pathway activity which led to tumor suppression. “Our study results suggest a new drug cocktail that is effective in both human lung cancer cell lines and fly models,” said Cagan.  

The researchers concluded from this current study that combining these two agents resulted in a synergistic suppression of tumor formation and it was similar to the synergy that has been observed in human A549 lung adenocarcinoma cells. Fluvastatin was found to act both within transformed cells and to reduce whole-body trametinib toxicity in flies, according to the researchers.

Lung cancer remains the second most common cancer in both men and women, according to the American Cancer Society. It is often discovered too late to be treated successfully, and current therapies are highly toxic. Researchers have attempted to identify targeted therapies that are effective and do not harm unaffected tissues. With these two agents already FDA-approved, this may be an advantage when conducting human trials in the near future.