Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Statin as Repurposed Drug in Ovarian Cancer: A Comprehensive Review

Author(s): Asmara Ahmad, Sadia Javed* and Shumaila Kiran

Volume 29, Issue 27, 2023

Published on: 21 September, 2023

Page: [2116 - 2123] Pages: 8

DOI: 10.2174/1381612829666230913113808

Price: $65

conference banner
Abstract

With a prevalence rate of 6.6 per 100,000 women, ovarian cancer is the third most lethal gynecological tumor in the world. Several factors like family history, nulliparity, late menopause, genetic mutation, and an unhealthy lifestyle contribute to increasing the risk of ovarian cancer development. Novel research studies suggest that ovarian cancer may be caused by changes in the lipid metabolic profile that trigger inflammatory responses. Moreover, ovarian cancer patients will eventually experience chemoresistance. Statin, a competitive inhibitor of HMG-CoA reductase that is a lipid-lowering drug with pleiotropic effects, seems to be the best choice to deal with this therapeutic issue. The aim of this review is to highlight the pharmacotherapeutic potential of statins, especially the repurposing of statin drugs for antitumor mechanisms. This review will also provide a brief summary of the meta-analysis, and case-control observational studies carried out to examine the impact of statins on risk reduction and survival in ovarian cancer patients. Furthermore, this review will discuss the nanotechnological approach for improving the drug's bioavailability and safe and targeted delivery with controlled release of active ingredients, making statins more effective in preventing and treating ovarian cancer.

Keywords: Antitumor, epithelial ovarian cancer, mevalonate pathway, statin, Rho, fatality rate, lovastatin.

« Previous Next »
[1]
Wang Y, Ren F, Song Z, Chen P, Liu S, Ouyang L. Statin use and the risk of ovarian and endometrial cancers: A meta-analysis. BMC Cancer 2019; 19(1): 730.
[http://dx.doi.org/10.1186/s12885-019-5954-0] [PMID: 31340777]
[2]
Huang J, Chan WC, Ngai CH, et al. Worldwide burden, risk factors, and temporal trends of ovarian cancer: A global study. Cancers 2022; 14(9): 2230.
[http://dx.doi.org/10.3390/cancers14092230] [PMID: 35565359]
[3]
Manzano-León N, Garcia-Lopez P. Statins as adjuvants in the treatment of ovarian cancer: Controversy and misunderstanding. Eur J Pharmacol 2021; 896: 173915.
[http://dx.doi.org/10.1016/j.ejphar.2021.173915] [PMID: 33513335]
[4]
Majidi A, Na R, Dixon-Suen S, Jordan SJ, Webb PM. Common medications and survival in women with ovarian cancer: A systematic review and meta-analysis. Gynecol Oncol 2020; 157(3): 678-85.
[http://dx.doi.org/10.1016/j.ygyno.2020.03.028] [PMID: 32317171]
[5]
Stewart C, Ralyea C, Lockwood S. Ovarian cancer: An integrated review. Semin Oncol Nurs 2019; 35(2): 151-6.
[http://dx.doi.org/10.1016/j.soncn.2019.02.001] [PMID: 30867104]
[6]
Irvin S, Clarke MA, Trabert B, Wentzensen N. Systematic review and meta-analysis of studies assessing the relationship between statin use and risk of ovarian cancer. Cancer Causes Control 2020; 31(10): 869-79.
[http://dx.doi.org/10.1007/s10552-020-01327-8] [PMID: 32685996]
[7]
Chimento A, Casaburi I, Avena P, et al. Cholesterol and its metabolites in tumor growth: Therapeutic potential of statins in cancer treatment. Front Endocrinol 2019; 9: 807.
[http://dx.doi.org/10.3389/fendo.2018.00807] [PMID: 30719023]
[8]
Iannelli F, Lombardi R, Milone MR, et al. Targeting mevalonate pathway in cancer treatment: Repurposing of statins. Recent Pat Anticancer Drug Discovery 2018; 13(2): 184-200.
[http://dx.doi.org/10.2174/1574892812666171129141211] [PMID: 29189178]
[9]
Beckwitt CH, Brufsky A, Oltvai ZN, Wells A. Statin drugs to reduce breast cancer recurrence and mortality. Breast Cancer Res 2018; 20(1): 144.
[http://dx.doi.org/10.1186/s13058-018-1066-z] [PMID: 30458856]
[10]
Osmak M. Statins and cancer: Current and future prospects. Cancer Lett 2012; 324(1): 1-12.
[http://dx.doi.org/10.1016/j.canlet.2012.04.011] [PMID: 22542807]
[11]
Barbalata CI, Tefas LR, Achim M, Tomuta I, Porfire AS. Statins in risk-reduction and treatment of cancer. World J Clin Oncol 2020; 11(8): 573-88.
[http://dx.doi.org/10.5306/wjco.v11.i8.573] [PMID: 32879845]
[12]
Hindler K, Cleeland CS, Rivera E, Collard CD. The role of statins in cancer therapy. Oncologist 2006; 11: 306-15.
[http://dx.doi.org/10.1634/theoncologist.11-3-306]
[13]
Bian Y, Tingting H, Zehui L, et al. Bone tissue engineering for treating osteonecrosis of the femoral head. Exploration 2023; 3(2): 20210105.
[http://dx.doi.org/10.1002/EXP.20210105]
[14]
Kodach LL, Jacobs RJ, Voorneveld PW, et al. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ‘stemness’ via the bone morphogenetic protein pathway. Gut 2011; 60(11): 1544-53.
[http://dx.doi.org/10.1136/gut.2011.237495] [PMID: 21551187]
[15]
Jiang W, Hu JW, He XR, Jin WL, He XY. Statins: A repurposed drug to fight cancer. J Exp Clin Cancer Res 2021; 40(1): 241.
[http://dx.doi.org/10.1186/s13046-021-02041-2] [PMID: 34303383]
[16]
Rao PS, Rao US. Statins decrease the expression of c-Myc protein in cancer cell lines. Mol Cell Biochem 2021; 476(2): 743-55.
[http://dx.doi.org/10.1007/s11010-020-03940-2] [PMID: 33070276]
[17]
Zaleska M, Mozenska O, Bil J. Statins use and cancer: An update. Future Oncol 2018; 14(15): 1497-509.
[http://dx.doi.org/10.2217/fon-2017-0543] [PMID: 29722274]
[18]
Patra KC, Hay N. The pentose phosphate pathway and cancer. Trends Biochem Sci 2014; 39(8): 347-54.
[http://dx.doi.org/10.1016/j.tibs.2014.06.005] [PMID: 25037503]
[19]
Harding BN, Delaney JA, Urban RR, Weiss NS. Use of statin medications following diagnosis in relation to survival among women with ovarian cancer. Cancer Epidemiol Biomarkers Prev 2019; 28(7): 1127-33.
[http://dx.doi.org/10.1158/1055-9965.EPI-18-1194]
[20]
Taylor-Harding B, Orsulic S, Karlan BY, Li AJ. Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. Gynecol Oncol 2010; 119(3): 549-56.
[http://dx.doi.org/10.1016/j.ygyno.2010.08.017] [PMID: 20837358]
[21]
Gauthaman K, Fong CY, Bongso A. Statins, stem cells, and cancer. J Cell Biochem 2009; 106(6): 975-83.
[http://dx.doi.org/10.1002/jcb.22092] [PMID: 19224538]
[22]
Martirosyan A, Clendening JW, Goard CA, Penn LZ. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: Potential therapeutic relevance. BMC Cancer 2010; 10(1): 103.
[http://dx.doi.org/10.1186/1471-2407-10-103] [PMID: 20298590]
[23]
Stine JE, Guo H, Sheng X, et al. The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Oncotarget 2016; 7(1): 946-60.
[http://dx.doi.org/10.18632/oncotarget.5834] [PMID: 26503475]
[24]
Elmore RG, Ioffe Y, Scoles DR, Karlan BY, Li AJ. Impact of statin therapy on survival in epithelial ovarian cancer. Gynecol Oncol 2008; 111(1): 102-5.
[http://dx.doi.org/10.1016/j.ygyno.2008.06.007] [PMID: 20698078]
[25]
Dorsch M, Kowalczyk M, Planque M, et al. Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis. Cell Rep 2021; 37(8): 110056.
[http://dx.doi.org/10.1016/j.celrep.2021.110056] [PMID: 34818551]
[26]
Rybstein MD, Bravo-San Pedro JM, Kroemer G, Galluzzi L. The autophagic network and cancer. Nat Cell Biol 2018; 20(3): 243-51.
[http://dx.doi.org/10.1038/s41556-018-0042-2] [PMID: 29476153]
[27]
Narita M, Young ARJ, Narita M. Autophagy facilitates oncogene-induced senescence. Autophagy 2009; 5(7): 1046-7.
[http://dx.doi.org/10.4161/auto.5.7.9444] [PMID: 19652542]
[28]
Wang KH, Liu CH, Ding DC. Statins as repurposed drugs in gynecological cancer: A review. Int J Mol Sci 2022; 23(22): 13937.
[http://dx.doi.org/10.3390/ijms232213937] [PMID: 36430409]
[29]
Kobayashi Y, Kashima H, Rahmanto YS, et al. Drug repositioning of mevalonate pathway inhibitors as antitumor agents for ovarian cancer. Oncotarget 2017; 8(42): 72147-56.
[http://dx.doi.org/10.18632/oncotarget.20046] [PMID: 29069775]
[30]
Baandrup L, Dehlendorff C, Friis S, Olsen JH, Kjær SK. Statin use and risk for ovarian cancer: A Danish nationwide case–control study. Br J Cancer 2015; 112(1): 157-61.
[http://dx.doi.org/10.1038/bjc.2014.574] [PMID: 25393364]
[31]
Robinson E, Nandi M, Wilkinson LL, Arrowsmith DM, Curtis ADM, Richardson A. Preclinical evaluation of statins as a treatment for ovarian cancer. Gynecol Oncol 2013; 129(2): 417-24.
[http://dx.doi.org/10.1016/j.ygyno.2013.02.003] [PMID: 23402903]
[32]
Akinwunmi B, Vitonis AF, Titus L, Terry KL, Cramer DW. Statin therapy and association with ovarian cancer risk in the New England case control (NEC) study. Int J Cancer 2019; 144(5): 991-1000.
[http://dx.doi.org/10.1002/ijc.31758] [PMID: 30006925]
[33]
Mei Z, Liang M, Li L, Zhang Y, Wang Q, Yang W. Effects of statins on cancer mortality and progression: A systematic review and meta-analysis of 95 cohorts including 1,111,407 individuals. Int J Cancer 2017; 140(5): 1068-81.
[http://dx.doi.org/10.1002/ijc.30526] [PMID: 27859151]
[34]
Markowska A, Antoszczak M, Markowska J, Huczyński A. Statins: HMG-CoA reductase inhibitors as potential anticancer agents against malignant neoplasms in women. Pharmaceuticals 2020; 13(12): 422.
[http://dx.doi.org/10.3390/ph13120422] [PMID: 33255609]
[35]
Korani S, Korani M, Bahrami S, et al. Application of nanotechnology to improve the therapeutic benefits of statins. Drug Discovery Today 2019; 24(2): 567-74.
[http://dx.doi.org/10.1016/j.drudis.2018.09.023] [PMID: 30292917]
[36]
Sirtori CR. The pharmacology of statins. Pharmacol Res 2014; 88: 3-11.
[http://dx.doi.org/10.1016/j.phrs.2014.03.002] [PMID: 24657242]
[37]
Meor Anuar Shuhaili MFR, Samsudin IN, Stanslas J, Hasan S, Thambiah SC. Effects of different types of statins on lipid profile: A perspective on Asians. Int J Endocrinol Metab 2017; In Press(In Press): e43319.
[http://dx.doi.org/10.5812/ijem.43319] [PMID: 28848611]
[38]
Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: The past and the future. Adv Drug Deliv Rev 2013; 65(1): 104-20.
[http://dx.doi.org/10.1016/j.addr.2012.10.003] [PMID: 23088863]
[39]
Safwat S, Ishak RA, Hathout RM, Mortada ND. Statins anticancer targeted delivery systems: Re-purposing an old molecule. J Pharm Pharmacol 2017; 69: 613-24.
[http://dx.doi.org/10.1111/jphp.12707]
[40]
Wang J, Chen J, Ye N, et al. Absorption, pharmacokinetics and disposition properties of solid lipid nanoparticles (SLNs). Curr Drug Metab 2012; 13(4): 447-56.
[http://dx.doi.org/10.2174/138920012800166553] [PMID: 22443539]
[41]
Tuerdi N, Anwaier G, Zhang X, et al. Simvastatin nanoliposome induces myocardial and hepatic toxicities due to its absorption enhancement in mice. Asian J Pharm Sci 2020; 15(1): 112-20.
[http://dx.doi.org/10.1016/j.ajps.2019.02.002] [PMID: 32175023]
[42]
Prat J. New insights into ovarian cancer pathology. Ann Oncol 2012; 23: x111-7.
[http://dx.doi.org/10.1093/annonc/mds300]
[43]
Abdullah MI, Abed MN, Richardson A. Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells. Sci Rep 2017; 7: 8090.
[http://dx.doi.org/10.1038/s41598-017-08649-9]
[44]
Majidi A, Na R, Jordan SJ, De Fazio A, Webb PM, OPAL Study Group. Statin use and survival following a diagnosis of ovarian cancer: A prospective observational study. Int J Cancer 2021; 148: 1608-15.
[http://dx.doi.org/10.1002/ijc.33333]
[45]
Couttenier A, Lacroix O, Vaes E, Cardwell CR, De Schutter H, Robert A. Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study. PLoS ONE 2017; 12: e0189233.
[http://dx.doi.org/10.1371/journal.pone.0189233]
[46]
Lavie O, Pinchev M, Rennert HS, Segev Y, Rennert G. The effect of statins on risk and survival of gynecological malignancies. Gynecol Oncol 2013; 130: 615-9.
[http://dx.doi.org/10.1016/j.ygyno.2013.05.025]

Rights & Permissions Print Cite
Article Metrics
21
2
Wayfinder Image
World Mental Health Day
© 2024 Bentham Science Publishers | Privacy Policy