aSIRTing Control over Cancer Stem Cells
ABSTRACT Cancer stem cells lie at the root of chronic myelogenous leukemia (CML) and mediate its continued growth. Their resistance to current therapies results in an inability to eradicate the disease. In this issue of Cancer Cell, Li et al. identify SIRT1 as a new target for eliminating CML cancer stem cells.
- SourceAvailable from: Varun Vijay Prabhu[Show abstract] [Hide abstract]
ABSTRACT: Introduction: Cancer stem cells (CSCs) are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance and therapeutic resistance. Restoring wild-type (WT) p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target CSCs. Areas covered: This review covers the therapeutic approaches to restore the function of WT p53, cancer and normal stem cell biology in relation to p53 and the downstream effects of p53 on CSCs. Expert opinion: The restoration of WT p53 function by targeting p53 directly, its interacting proteins or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and CSCs based on the current evidence linking p53 signaling with these populations.Expert Opinion on Therapeutic Targets 11/2012; 16(12). DOI:10.1517/14728222.2012.726985
- [Show abstract] [Hide abstract]
ABSTRACT: Aging is a degenerative process resulting in compromised tissue maintenance and increased susceptibility to diseases, such as cancer. Recent advancements support the notion that aging is a highly regulated process governed by evolutionarily conserved pathways. In mammals, tissue-specific adult stem cells (ASCs) persist throughout the lifetime to maintain and repair tissues. While reduced ASC self-renewal is thought to contribute to compromised tissue maintenance, increased self-renewal of cancer stem cells (CSCs) may lead to tumorigenesis. It is speculated that genetic regulators of aging, such as sirtuins, are likely to impinge upon the ASC compartments to regulate tissue maintenance and tumorigenesis. In this review, we discuss the emerging evidence linking sirtuins to normal and malignant ASC self-renewal, tissue maintenance, and tumorigenesis.Genes & cancer 03/2013; 4(3-4):76-81. DOI:10.1177/1947601912474930