[Frontiers in Bioscience 16, 952-961, January 1, 2011]

Investigations of survivin: the past, present and future

Chun Hei Antonio Cheung1, LiTing Cheng2, Kwang-Yu Chang1, Huang-Hui Chen1, Jang-Yang Chang1, 3

1 National Institute of Cancer Research, National Health Research Institutes (NHRI), Tainan 70456, Taiwan R.O.C., 2Graduate Institute of Animal Vaccine Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan R.O.C., 3Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70456, Taiwan R.O.C

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Survivin
3.1. The expression of survivin in human cancers
3.2. Molecular functions of survivin
3.3. Survivin and drug resistance
3.4. Targeting survivin by anti-sense, siRNA and dominant-negative constructs
3.5. Recent developments of the survivin specific small molecule inhibitors
4. Summary and perspective
5. Acknowledgements
6. References

1. ABSTRACT

Survivin is a member of the inhibitors-of-apoptosis protein (IAPs) family. It promotes cell survival through interference with multiple cell cycle-related proteins such as INCENP and Aurora B kinase. Survivin also inhibits cell death through interference with both caspase-dependent and -independent cell apoptosis. Interestingly, recent evidence suggests that survivin may also play a role in the regulation of cancer cell autophagy. At the clinical level, studies on clinical specimens have shown that survivin expression is up-regulated in various human cancers and its up-regulation is associated with tumour resistance to both chemotherapy and radiation therapy. On the basis of these findings, survivin has been proposed as an attractive target for new anti-cancer interventions. However, despite the role that survivin plays in cancer cell survival and anti-drug response, the development of survivin inhibitors is relatively slow as compared to other therapeutic inhibitors for cancer treatment. In this review, the relationships between survivin expression and the causation of drug resistance in cancers are re-addressed. This review also summarizes the recent development of survivin inhibitors for clinical usage.