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. 2013 Mar;4(3-4):82-90.
doi: 10.1177/1947601912473826.

Emerging Roles of SIRT1 in Cancer Drug Resistance

Zhiqiang Wang  1 , Wenyong Chen
Affiliations

Emerging Roles of SIRT1 in Cancer Drug Resistance

Zhiqiang Wang et al. Genes Cancer. 2013 Mar.

Abstract

Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, acquired resistance has emerged as a daunting challenge to targeted cancer therapy, which abolishes the efficacy of otherwise successful targeting drugs. Cancer cells gain the resistance property through a variety of mechanisms in primary and metastatic cancers, involving cellular intrinsic and extrinsic factors. Increasing evidence suggests that the mammalian stress response gene sirtuin 1 (SIRT1) plays a critical role in multiple aspects of cancer drug resistance. SIRT1 decreases drug penetration, confers proliferation and antiapoptotic survival advantages to cancer cells, facilitates acquired resistance through genetic mutations, promotes the survival of cancer stem cells, and changes the tumor microenvironment for resistance in cell-autonomous and -nonautonomous manners. This article provides an overview of research advances in the roles of SIRT1 in cancer drug resistance and highlights the prospect of targeting SIRT1 as a new strategy to overcome cancer drug resistance and improve therapeutic outcomes.

Keywords: SIRT1; acquired resistance; cancer stem cells; drug resistance; genetic mutation; tumor microenvironment.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Regulation of SIRT1 expression and enzymatic activity. SIRT1 is subjected to multiple layers of regulation from transcription and translation to protein functions in cancer cells as detailed in the text.
Figure 2.
Figure 2.
SIRT1 regulates multiple pathways of cancer drug resistance. Overexpression of SIRT1 in cancer cells reduces drug penetration, confers cell proliferation and antiapoptotic advantages, promotes DNA damage repair and acquisition of genetic mutations under therapeutic stress, increases the gain of function of cancer stem cell properties, and modulates the tumor microenvironment for cancer cell drug resistance.
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