Statins in risk-reduction and treatment of cancer

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Abstract

Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer ( i.e., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

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Use of statins and the risk of death in patients with prostate cancer.

Oriana HY Yu, Maria Eberg, Serge Benayoun … (2014)

To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.

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The role of cholesterol metabolism in cancer.

Xiao Ding, Weihua Zhang, Song Li … (2019)

Cholesterol plays an important role in cancer development. Both clinical and experimental studies have found that hypercholesterolemia and a high-fat high-cholesterol diet can affect cancer development. External cholesterol can directly activate the oncogenic Hedgehog pathway, and internal cholesterol can induce mTORC1 signaling. Cholesterol is a key component of lipid rafts, which are the major platforms for signaling regulation in cancer, and chelating membrane cholesterol is an effective anti-cancer strategy that disrupts the functions of lipid rafts. Cholesterol metabolism is often reprogrammed in cancer cells. Targeting cholesterol metabolism as a new therapeutic approach has received increasing attention. Here, we summarize some key molecular mechanisms supporting the use of anti-cholesterol therapy for cancer treatment.

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International incidence and mortality trends of liver cancer: a global profile

Martin C. S. Wong, Johnny Y Jiang, William Goggins … (2017)

We examined the global incidence and mortality rates of liver cancer, and evaluated the association between incidence/mortality and socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP]) using linear regression analysis. The average annual percent change (AAPC) of the trends was evaluated from join-point regression analysis. The global incidence of liver cancer varied widely by nine-fold, and was negatively correlated with HDI (men: r = −0.232, p = 0.003; women: r = −0.369, p < 0.001) and GDP per capita (men: r = −0.164, p = 0.036; women: r = −0.212, p = 0.007). Its mortality showed a similarly negative correlation with both indices. The greatest incidence rise in men was observed in Poland (AAPC = 17.5, 95% C.I. = 5.6, 30.9) and Brazil (AAPC = 13.2, 95% C.I. = 5.9, 21.0), whereas Germany (AAPC = 6.6, 95% C.I = 2.0, 11.5) and Norway (AAPC = 6.5, 95% C.I. = 3.2, 10.0) had the greatest increase in women. The mortality rates paralleled the incidence rates in most countries. For mortality, Malta (AAPC = 11.5, 95% C.I. = 3.9, 19.8), Australia (AAPC = 6.8, 95% C.I. = 2.2, 11.5) and Norway (APCC = 5.6, 95% C.I. = 2.8, 8.5) reported the biggest increase among men; whilst Australia (AAPC = 13.4, 95% C.I. = 7.8, 19.4) and Singapore (AAPC = 7.7, 95% C.I. = 4.1, 11.5) showed the most prominent rise among women. These epidemiological data identified countries with potentially increasing trends of liver cancer for preventive actions.

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Author and article information

Contributors

Cristina I Barbalata

Lucia R Tefas

Marcela Achim

Ioan Tomuta

Alina S Porfire

Journal

Journal ID (nlm-ta): World J Clin Oncol

Journal ID (publisher-id): WJCO

Title: World Journal of Clinical Oncology

Publisher: Baishideng Publishing Group Inc

ISSN (Electronic): 2218-4333

Publication date (Print): 24 August 2020

Publication date (Electronic): 24 August 2020

Volume: 11

Issue: 8

Pages: 573-588

Affiliations

Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania

Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania. aporfire@ 123456umfcluj.ro

Author notes

Author contributions: Barbalata CI wrote the manuscript with support from Tefas LR, Achim M and Porfire AS; Porfire AS and Barbalata CI conceived the idea and organized the manuscript; Porfire AS and Tomuta I supervised the project and approved the final manuscript.

Corresponding author: Alina S Porfire, PhD, Associate Professor, Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu- Hatieganu” University of Medicine and Pharmacy, 41 Victor Babes, Cluj-Napoca 400012, Romania. aporfire@ 123456umfcluj.ro

Article

Other ID: jWJCO.v11.i8.pg573

DOI: 10.5306/wjco.v11.i8.573

PMC ID: 7443827

PubMed ID: 32879845

SO-VID: fdda1321-621e-49a2-a25b-a8301eb02ec7

License:

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

History

Date received : 28 February 2020

Date revision received : 18 May 2020

Date accepted : 10 June 2020

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Statins in risk-reduction and treatment of cancer

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Cancer Metabolism

Most cited references 92

Use of statins and the risk of death in patients with prostate cancer.

The role of cholesterol metabolism in cancer.

International incidence and mortality trends of liver cancer: a global profile

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Cited by 24

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