HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence?

Abstract

Statins have been shown to possess properties that go beyond their lipid-lowering effects. These agents act on the mevalonate pathway and inhibit synthesis of cholesterol, geranylgeranyl pyrophosphate, and farnesyl pyrophosphate, which are necessary for posttranslational modification of the Rho, Rac, and Ras superfamily of proteins. Early phase studies have demonstrated that this modulation of cellular signaling can ultimately exert pro-apoptotic, anti-angiogenic, and immunomodulatory effects, and might even restore chemosensitivity in several hematologic cancers. Nonetheless, these promising preclinical results have not yet migrated from the bench to the bedside as their effectiveness as adjuvant agents in hematologic malignancies is currently uncertain. In the present review, we summarize the existing evidence stemming from preclinical and clinical studies pertaining to the use of statins as adjuvant therapies in hematologic malignancies, and discuss the new insights gained from the ongoing translational research.

Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

“…GGPP and FPP are important modulators of Rho GTPases. Interestingly, there are encouraging reports that the incidence of cancer is reduced in statin users [73, 74]. Study indicates that Simvastatin sensitizes the tumor xenotransplants from FaDu (Hypopharynx Squamous cell carcinoma) cells and A431, a vulvar squamous cell carcinoma derived cell line [75].…”

Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention

“…Although not currently part of medical therapy for malignancy, a potential tumor-suppressor and anti-cancer role for statins thought to be independent of their lipidreducing properties is also emerging. Statin use is associated with reduced incidence of colorectal, liver, breast, skin, prostate, melanoma, head and neck, lung and pancreatic cancers [136–140]. Statins also inhibit production of the mevalonate pathway products involved in posttranslational modification of cell signaling proteins.…”

“…Statins also inhibit production of the mevalonate pathway products involved in posttranslational modification of cell signaling proteins. This modulation of cellular signaling may have pro-apoptotic, antiproliferative, anti-invasive, and radiosensitizing effects [23,135,136]. Statins may also play a protective role against DNA damage which is a key factor in pathophysiology of both atherosclerosis and cancer [141].…”

Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again

“…2). Ultimately, this leads to decreased cellular proliferation and induction of apoptosis, which has been demonstrated in several preclinical models [29][30][31]. In addition, there is evidence of mevalonate pathway-independent effects of statins, including direct inhibition of the Akt and Raf signaling pathways and activation of the tumor suppressor p53.…”

“…This pathway is not only responsible for membrane and glycoprotein synthesis but also results in protein isoprenylation, a process that is required for proper functioning of cell signaling cascades including those of the Ras oncoprotein. Reproduced from [31] with permission from the publisher. Abbreviations: Cdc42, cell division control protein 42 homolog; CoA, coenzyme A; HMG, 3-hydroxy-3-methylglutaryl; PI3K, phosphatidylinositol 3-kinase; PLC, phospholipase C. a major metabolite of PGE 2 , had a longer survival than those with no change or an increase in urinary PGE-M (14.8 vs. 6.3 vs. 5.0 months) [60].…”