» Articles » PMID: 27308369

Targeting Tumor Cell Metabolism Via the Mevalonate Pathway: Two Hits Are Better Than One

Overview
Journal Mol Cell Oncol
Specialty Oncology
Date 2016 Jun 17
PMID 27308369
Citations 6
Authors
Affiliations
Soon will be listed here.
Abstract

Statins are promising anticancer agents that target the mevalonate pathway. Tumor cells are sensitive to depletion of mevalonate-derived products but this activity triggers a homeostatic feedback loop that blunts statin efficacy. We showed that dipyridamole inhibits this feedback response and potentiates statin antitumor activity. This study identifies statins plus dypridamole as a preclinically effective combination of approved agents.

Citing Articles

Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.

Irie N, Mizoguchi K, Warita T, Nakano M, Sasaki K, Tashiro J Biomedicines. 2024; 12(3).

PMID: 38540310 PMC: 10968169. DOI: 10.3390/biomedicines12030698.


Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women.

Yang J, Stack M Cancers (Basel). 2020; 12(11).

PMID: 33233362 PMC: 7700662. DOI: 10.3390/cancers12113469.


Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells.

Gobel A, Breining D, Rauner M, Hofbauer L, Rachner T Cell Death Dis. 2019; 10(2):91.

PMID: 30692522 PMC: 6349912. DOI: 10.1038/s41419-019-1322-x.


Epidemiologic Analysis Along the Mevalonate Pathway Reveals Improved Cancer Survival in Patients Who Receive Statins Alone and in Combination With Bisphosphonates.

El-Refai S, Brown J, Arnold S, Black E, Leggas M, Talbert J JCO Clin Cancer Inform. 2019; 1:1-12.

PMID: 30657380 PMC: 6467073. DOI: 10.1200/CCI.17.00010.


The isomiR-140-3p-regulated mevalonic acid pathway as a potential target for prevention of triple negative breast cancer.

Bhardwaj A, Singh H, Trinidad C, Albarracin C, Hunt K, Bedrosian I Breast Cancer Res. 2018; 20(1):150.

PMID: 30537987 PMC: 6290546. DOI: 10.1186/s13058-018-1074-z.


References
1.
Clendening J, Pandyra A, Boutros P, El Ghamrasni S, Khosravi F, Trentin G . Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010; 107(34):15051-6. PMC: 2930553. DOI: 10.1073/pnas.0910258107. View

2.
Ahern T, Pedersen L, Tarp M, Cronin-Fenton D, Garne J, Silliman R . Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J Natl Cancer Inst. 2011; 103(19):1461-8. PMC: 3186780. DOI: 10.1093/jnci/djr291. View

3.
Clendening J, Pandyra A, Li Z, Boutros P, Martirosyan A, Lehner R . Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma. Blood. 2010; 115(23):4787-97. DOI: 10.1182/blood-2009-07-230508. View

4.
Clendening J, Penn L . Targeting tumor cell metabolism with statins. Oncogene. 2012; 31(48):4967-78. DOI: 10.1038/onc.2012.6. View

5.
Pandyra A, Mullen P, Kalkat M, Yu R, Pong J, Li Z . Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Res. 2014; 74(17):4772-82. DOI: 10.1158/0008-5472.CAN-14-0130. View