# Unraveling the Potential Pathogenic Role of Squalene Synthase (SQS) in Lung Cancer Using Enzyme Inhibitors as Molecular Tools

## TL;DR

This study explores how inhibiting the enzyme squalene synthase (SQS) could be a new treatment for lung cancer.

## Contribution

The paper provides new evidence that SQS is a viable drug target in lung cancer using enzyme inhibitors.

## Key findings

- SQS inhibition reduced lung inflammation and tumor burden in animal models.
- Two SQS inhibitors showed anticancer effects in cell-based assays.
- SQS inhibitors may offer a novel approach for targeting lung cancer.

## Abstract

Squalene synthase
(SQS) is a key enzyme in the mevalonate
pathway,
catalyzing the first committed step in cholesterol biosynthesis. Several
small-molecule SQS inhibitors have been developed thus far, initially
aiming at treating hypercholesterolemia. Although their development
for cardiovascular diseases was limited after clinical trials compared
with statins, the potential of SQS as an anticancer target has recently
gained renewed attention. Nevertheless, the evaluation of SQS inhibitors
as anticancer agents has been rudimentary thus far. Herein, we attempted
to provide some clear evidence of the potential of this enzyme as
a “druggable” target in lung cancer. Accordingly, two
chemically diverse SQS inhibitors were used as pharmacological tools
and tested in different cancer-cell-based assays, providing some groundwork
for their mechanistic underpinning in cancer cells. Lastly, in vivo studies corroborated the potent effect of SQS inhibition
on lung inflammation and tumor burden, rendering SQS as a viable and
promising drug target against lung cancer.