Survivin as a Therapeutic Target for the Treatment of Human Cancer.

Simple Summary: Survivin is overexpressed in a wide variety of human cancers and is associated with increased chemotherapy resistance, recurrence, and shorter patient survival. Although survivin was first identified as an inhibitor of apoptosis based on its sequence homology, recent studies show that survivin primarily plays a role in the regulation of cell division, as a component of the chromosome passenger complex, which can be localized to the centromere, the spindle midzone, or midbody in a cell cycle-dependent manner. Disruption of survivin function generally leads to mitotic catastrophe and is associated with elevated levels of aneuploidy. In contrast, ectopic expression of survivin can promote cell survival under certain conditions and is implicated in mediating resistance to various cancer drugs, possibly by interactions with molecules that modulate apoptotic pathways. A potential role of survivin in the regulation of mitochondrial functions and processes of autophagy has emerged. Because of its prevalent overexpression in cancer and very limited expression in normal tissues, survivin has been proposed as an ideal therapeutic target, and various approaches have been investigated for survivin inhibition. Here we provide a critical review of our current understanding of the role of survivin in promoting malignancy and strategies for the development of survivin-targeted therapy for cancer. Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and acts as an essential mediator of mitotic progression. Other potential functions of survivin, such as mitochondrial function and autophagy, have also been proposed. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rates in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as the efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer. [ABSTRACT FROM AUTHOR]

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