Emerging role of sirtuins in breast cancer metastasis and multidrug resistance: Implication for novel therapeutic strategies targeting sirtuins

Sirtuins (SIRTs), a class III histone deacetylases (HDACs) that require NAD+ as a cofactor and include SIRT1-7 proteins in mammals. Accumulative evidence has established that every sirtuin possesses exclusive and poised biology, implicating their role in the regulation of multifaceted biological functions leading to breast cancer initiation, progression, and metastasis. This article provides an outline of recent developments in the role of sirtuins in breast cancer metastasis and development of multidrug resistance (MDR). In addition, we have also highlighted the impending prospects of targeting SIRTs to overcome MDR to bring advancement in breast cancer management. Further, this review will focus on strategies for improving the activity and efficacy of existing cancer therapeutics by combining (adjuvant treatment/therapy) them with sirtuin inhibitors/modulators. All available as well as newly discovered synthetic and dietary sirtuin inhibitors, activators/modulators have been extensively reviewed and compiled to provide a rationale for targeting sirtuins. Further, we discuss their potential in developing future therapeutics against sirtuins proposing their use along with conventional chemotherapeutics to overcome the problem of breast cancer metastasis and MDR.