Possibilities of using statins in comprehensive antitumor treatment

Abstract

Frequency of atherosclerosis significantly increases with age, same as malignant tumor morbidity. Concurrent pathology (including in the cardiovascular system) affects selection of antitumor treatment limiting use of cardiotoxic (though highly effective) drugs. Statins are the main treatment for atherosclerosis but their study showed that regulation of cholesterol metabolism affects functioning of tumor cells. According to the results of clinical trial meta-analyses, regular use of statins decreases mortality in patients with bladder, prostate, renal, ovarian, lung, breast, and colorectal cancer both due to decreased risk of cardiovascular complications and increased effectiveness of antitumor drugs. In some studies, decreased risk of liver, esophageal, endometrial, renal, gastric, and pancreatic cancers was observed in patients taking statins. Antitumor effects of statins are supposedly mediated by decreased cholesterol production which is used by tumor cells for functioning and membrane synthesis. Additionally, statins inactivate RAS and RHO oncogenes by suppressing their isoprenylation, inhibit proliferation of tumor cells. Statins also contribute to activation of antitumor immunity, increased ferroptosis and autophagy. Statins activate apoptosis by interacting with mitochondrial procaspase 9, inhibit expression of toll-like receptors (TLR4), NF-κB, tumor necrosis factor α, interleukins 1β and 6, suppress the mTOR pathway. Therefore, multifaceted direct and indirect antitumor effects of statins show that these pharmaceuticals should be more intently considered as a component of antitumor therapy.