Statins as Potential Therapeutics for Lung Cancer: Molecular Mechanisms and Clinical Outcomes

Lung cancer is the most common cancer worldwide. It also has the highest malignancy-associated mortality rate. Treatment options are limited by cancer and tumor heterogeneity, resistance to treatment options, and an advanced stage at time of diagnosis, all of which are common. Statins are a class of lipid-lowering medications that have been studied for their antitumor effects in various types of cancers. Multiple mechanisms have been proposed to explain their observed off-target effects. Most of these hypotheses focus largely on statin-induced upregulation of proapoptotic signaling pathways and mediators, and the downregulation of antineoplastic factors secondary to statin use. Preclinical and clinical studies support their use for conferring a mortality benefit and improving treatment effect in some chemotherapy-resistant subtypes of lung cancer. However, their exact mechanism of action, class-dependent effect, dose-dependent effect, potential use as adjuvant chemotherapeutics, and markers of statin-sensitivity in specific lung cancer subtypes remain areas of ongoing investigation. Herein, we review the latest literature pertinent to the role statins can play in the management of lung cancers.