Rational cotargeting of Pim-1 and Akt in prostate cancer.

Evaluation of: Cen B, Mahajan S, Wang W, Kraft AS. Elevation of receptor tyrosine kinases by small molecule AKT inhibitors in prostate cancer is mediated by Pim-1. Cancer Res. 73(11), 3402-3411 (2013). The PI3K/Akt pathway is a key pathway in many advanced and aggressive cancers. Targeted inhibition of this pathway is currently an actively pursued therapeutic strategy. However, blockade of this pathway with inhibitors has been challenging, with up-regulation of reciprocal feedback pathways contributing to treatment failures. The article evaluated presents mechanistic data on how Pim is a critical mediator of the receptor tyrosine elevation induced by Akt inhibition. Pim-1 kinases are overexpressed in resistant and aggressive cancers. Following Akt inhibition, Pim- regulates receptor tyrosine kinases up-regulation, at least in part, through a cap-independent translation. This research leads the way for further evaluation of co-targeting strategies using Pim-1 inhibitors in combination with PI3K/Akt pathway inhibitors.