Promising SINEs for Embargoing Nuclear-Cytoplasmic Export as an Anticancer Strategy

In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed. Significance: The nuclear transport mechanism is dysregulated in many malignancies and is associated with dysfunction of many regulatory proteins. Targeting this mechanism as an anticancer strategy has been compelling, and novel agents that selectively inhibit the nuclear export pathway have demonstrated preliminary evidence of clinical efficacy with an acceptable safety profile. (C) 2014 AACR.