Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

The acquired resistance of human cancer cells to apoptosis is one of the defining hallmarks of cancer. Upregulated expression of inhibitors of apoptosis proteins (IAP) has been implicated in drug resistance in several cancers. Survivin (encoded by BIRC5), the smallest member of the IAP family, has been correlated with both the control of cell apoptosis and regulation of cell mitosis in cancer. Owing to its critical role in regulation of cell survival and development of cancer resistance, as well as its distinguishingly high level of expression in many types of cancer, survivin has long been regarded as a promising therapeutic target for cancer therapy. This review first presents an overview of the mechanism by which survivin regulates cell function, followed by a discussion of the current state of survivin-targeted therapies. We focus on the application of nanoparticulate systems to deliver survivin inhibitors, co-delivery of survivin inhibitors with chemotherapeutic agents, synchronous targeting of survivin, other drug resistant molecules, and survivin regulators. We conclude by highlighting the current limitations associated with survivin-targeted therapies and speculating on the future strategies to surmount these impediments. (C) 2016 Elsevier B.V. All rights reserved.