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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Therapeutic Agents: Other

Abstract C170: The combination of statins and dipyridamole is effective preclinically in AML, MM, and breast cancer.

Aleksandra Pandyra, Paul Sobol, Sumaiya Sharmeen, Aaron Schimmer and Linda Penn
Aleksandra Pandyra
1Ontario Cancer Institute, Toronto, ON, Canada.
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Paul Sobol
1Ontario Cancer Institute, Toronto, ON, Canada.
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Sumaiya Sharmeen
1Ontario Cancer Institute, Toronto, ON, Canada.
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Aaron Schimmer
1Ontario Cancer Institute, Toronto, ON, Canada.
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Linda Penn
1Ontario Cancer Institute, Toronto, ON, Canada.
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DOI: 10.1158/1535-7163.TARG-11-C170 Published November 2011
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Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA

Abstract

Statins are drugs that have been utilized for years to treat hyperlipidemia through inhibition of the rate-limiting enzyme of the mevalonate (MVA) pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Preclinical evidence has demonstrated statins to possess anti-cancer properties against a wide range of tumors but not normal cells. Through the use of a chemical library screen, we hypothesize that the identification of compounds which potentiate the anti-cancer effects of statins will uncover novel molecular pathways and/or targets that can be exploited in combination with the MVA pathway to maximize tumor cell death.

A pilot 100-compound library, composed of off-patent pharmacologically active drugs clinically used for a wide spectrum of diseases was screened in the multiple myeloma (MM) KMS11 cell line. Dipyridamole (DP), a commonly prescribed anti-platelet agent potentiated the anti-cancer effects of atorvastatin. The DP-statin combination was synergistic and capable of inducing apoptosis in a variety of acute myelogenous leukemia (AML), MM and breast cancer cell lines. The DP-statin combination also induced apoptosis in primary AML patient samples, but was not toxic to normal PBSCs. In an in vivo AML tumor model, the DP-statin combination was found to be effective at inhibiting tumor growth.

DP is known to elicit numerous effects, amongst them, phosphodiesterase (PDE) inhibition. In AML cell lines, activators of the PKA pathway including other PDE inhibitors, also induced apoptosis in combination with statins similar to DP. Interestingly, the DP-statin combination prevented the increase of HMGCR, which occurs following statin treatment as part of a classic feedback response. Further mechanistic investigations to determine how DP potentiates statin-induced apoptosis are underway. As both statins and DP are pre-approved for use in humans, off-patent, and readily available, they have the potential to directly impact patient care.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C170.

  • Copyright © 2011, American Association for Cancer Research
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Molecular Cancer Therapeutics: 10 (11 Supplement)
November 2011
Volume 10, Issue 11 Supplement
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Abstract C170: The combination of statins and dipyridamole is effective preclinically in AML, MM, and breast cancer.
Aleksandra Pandyra, Paul Sobol, Sumaiya Sharmeen, Aaron Schimmer and Linda Penn
Mol Cancer Ther November 12 2011 (10) (11 Supplement) C170; DOI: 10.1158/1535-7163.TARG-11-C170

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Abstract C170: The combination of statins and dipyridamole is effective preclinically in AML, MM, and breast cancer.
Aleksandra Pandyra, Paul Sobol, Sumaiya Sharmeen, Aaron Schimmer and Linda Penn
Mol Cancer Ther November 12 2011 (10) (11 Supplement) C170; DOI: 10.1158/1535-7163.TARG-11-C170
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Therapeutic Agents: Other

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Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts

  • Abstract C068: Toward precision medicine for platinums
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  • Abstract C065: Dietary deprivation of non-essential amino acids improves anti-PD-1 immunotherapy in murine colon cancer
Show more Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts
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Molecular Cancer Therapeutics
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