Trametinib and fluvastatin combination could block non-small cell lung cancer pathway activity.
The combination of a melanoma drug recently approved by the FDA in combination with a cholesterol-lowering drug showed promise in treating non-small cell lung cancer (NSCLC).
Researchers from Icahn School of Medicine at Mount Sinai used a Drosophila fruit fly to develop a multi-gene lung cancer model for insight into tumor development. Analysis of fruit fly and human lung cancer cell lines allowed researchers to target 2 common genetic mutations, Ras and PTEN (P13K), which are most associated with NSCLC.
In building this model, researchers hoped to gain a better understanding of the mechanisms that promote tumors in NSCLC.
"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 lead researcher Ross Cagan, PhD. "This led to formation of tumor-like growths."
In a study published in Cell Report, researchers screened a library of 1192 FDA-approved drugs using a robotics-based approach. Researchers sought to find any suppressed tumors in the fly that could help improve overall survival, with several identified.
Investigators also examined 2 FDA-approved drugs called trametinib, used to treat melanoma, and fluvastatin, a common cholesterol lowering drug. When they administered each of these drugs orally, the drugs were found to inhibit Ras and P13K pathway activity. When the drugs were combined, it led to the suppression of tumor formation.
"Our study results suggest a new drug cocktail that is effective in both human lung cancer cell lines and fly models," Cagan said. "Next steps are to further explore this possibility in human trials in order to assess if it will help patients, but these 2 drugs make sense from a variety of studies and we find that they act together through multiple mechanisms to control cancer growth in the laboratory."
"These simple model systems can be useful for identifying new drug combinations that act in the context of the whole body,” Cagan continued. “Our goal is to leverage them as tools to help identify cocktails that are more effective and less toxic than current standard of care."