Statins as Anticancer Agents in the Era of Precision Medicine

Longo, Joseph; Leeuwen, Jenna E. van; Elbaz, Mohamad; Branchard, Emily; Penn, Linda Z.

doi:10.1158/1078-0432.ccr-20-1967

Cited by 117 publications

(122 citation statements)

References 113 publications

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“…However, oncologists often question the clinical relevance of statin effects on cancer cell lines in vitro, as the effective concentrations are 10-100 times greater than plasma levels (low to mid-nanomolar range) that are typically achieved in patients taking statins at the safest dose for hypercholesterolemia [21,22]. This has piqued interest in improving statin efficacy through combination strategies [23].…”

mentioning

confidence: 99%

Targeting the Mevalonate Pathway in Cancer

Juarez

Fruman

2021

Trends in Cancer

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confidence: 99%

Targeting the Mevalonate Pathway in Cancer

Juarez

Fruman

2021

Trends in Cancer

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“…They have also gained attention in cancer research due to their anti-tumor properties. Multiple lines of evidence indicate that certain cancers are highly dependent on the mevalonate pathway, and therefore, are vulnerable to statin treatment [ 16 , 17 ]. These drugs were found to inhibit the cell proliferation and induce the apoptosis in specific cancer cell types [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the most recent studies have shown the ability of some statins to inhibit endothelial-to-mesenchymal transition and sensitize cancer stem-like cells to chemotherapeutics [ 19 ]. It is important to emphasize that the observed in vivo and in vitro beneficial effects of the statin use are highly dependent on statin type, dose and treatment period [ 2 , 12 , 16 , 21 ]. Nevertheless, several observational and clinical trials demonstrated increased patient survival and reduced cancer recurrence after the statin therapy [ 16 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is important to emphasize that the observed in vivo and in vitro beneficial effects of the statin use are highly dependent on statin type, dose and treatment period [ 2 , 12 , 16 , 21 ]. Nevertheless, several observational and clinical trials demonstrated increased patient survival and reduced cancer recurrence after the statin therapy [ 16 , 20 , 21 ]. The variable pleiotropic anti-cancer effects reported for statins are to a great extent attributed to the reduced biosynthesis of isoprenoids and post-translational protein prenylation [ 2 , 16 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, several observational and clinical trials demonstrated increased patient survival and reduced cancer recurrence after the statin therapy [ 16 , 20 , 21 ]. The variable pleiotropic anti-cancer effects reported for statins are to a great extent attributed to the reduced biosynthesis of isoprenoids and post-translational protein prenylation [ 2 , 16 , 22 ]. Interestingly, individual statins were found to differentially modulate gene expression profiles in cancer cells, which may explain the observed variability in anti-cancer effects of these drugs [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies

Wujak

Kozakiewicz

Ciarkowska

et al. 2021

IJMS

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Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Studies on possible interactions between statins and human proteins could provide a deeper insight into the pleiotropic and adverse effects of these drugs. Adenylate kinase (AK) was found to regulate HDL endocytosis, cellular metabolism, cardiovascular function and neurodegeneration. In this work, we investigated interactions between human adenylate kinase isoenzyme 1 (hAK1) and atorvastatin (AVS), fluvastatin (FVS), pravastatin (PVS), rosuvastatin (RVS) and simvastatin (SVS) with fluorescence spectroscopy. The tested statins quenched the intrinsic fluorescence of hAK1 by creating stable hAK1-statin complexes with the binding constants of the order of 104 M−1. The enzyme kinetic studies revealed that statins inhibited hAK1 with significantly different efficiencies, in a noncompetitive manner. Simvastatin inhibited hAK1 with the highest yield comparable to that reported for diadenosine pentaphosphate, the only known hAK1 inhibitor. The determined AK sensitivity to statins differed markedly between short and long type AKs, suggesting an essential role of the LID domain in the AK inhibition. Our studies might open new horizons for the development of new modulators of short type AKs.

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Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

et al. 2022

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ImportanceEpidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.ObjectiveTo study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis–targeted therapies (ARATs).Data SourcesThis systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022.Study SelectionObservational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).Data Extraction and SynthesisTwo authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.Main Outcomes and MeasuresOverall mortality and prostate cancer–specific mortality (PCSM).ResultsTwenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes.Conclusions and RelevanceThe findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

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Statins as Anticancer Agents in the Era of Precision Medicine

Cited by 117 publications

References 113 publications

Targeting the Mevalonate Pathway in Cancer

Targeting the Mevalonate Pathway in Cancer

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

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