ReviewFoundationTargeting survivin for therapeutic discovery: past, present, and future promises

•Survivin is over-expressed in many cancers and an ideal target for drug discovery.•Survivin is considered “undruggable” due to lack of known enzymatic activities.•Targeting survivin expression has not been successful.•Targeting survivin-client interaction and its homo-dimerization is in the making.•Survivin has also been considered as a target for immunotherapy.

Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in cells of almost all cancers but not in most normal tissues in adults. Survivin expression is required for cancer cell survival and knocking down its expression or inhibiting its function using molecular approaches results in spontaneous apoptosis. Thus, survivin is an attractive and perhaps ideal target for cancer drug discovery. However, a US Food and Drug Administration (FDA)-approved drug targeting survivin has yet to emerge. In this Foundation Review, we examine and evaluate various strategies that have been used to target survivin and the stages of each survivin inhibitor to help understand this lack of success. We also provide future perspectives moving forward in targeting survivin for drug discovery.