Induction of Heat Shock Protein 70 as a Predictive Marker of the Tumor Cell Radiosensitization with Inhibitors of the Heat Shock Protein 90 Activity.

Abstract

Inhibitors of the heat shock protein 90 (HSP90) activity are considered as potential radiosensitizers of tumors with a perspective of their application in radiotherapy. However, there are tumors and tumor cell lines whose radioresistance is not decreased after treatment with the HSP90 activity inhibitors; therefore, a predictive marker is needed, which would allow one to predict the response of target cells. As such a marker, herein it is proposed to use induction of the heat shock protein 70 (HSP70) that is an early cellular response to the HSP90 dysfunction and can easily be immunodetected. It follows from the data obtained that the radiosensitization of HSP90 inhibitor-treated cells occurs only when this treatment causes the prominent induction of HSP70 in them. Determination of this marker enables one: 1) to predict a possibility of radiosensitization of any cells by means of the HSP90 activity inhibitors, 2) to design the inhibitor concentration range upon which the radiosensitizing effect seems likely to occur, 3) to find whether this radiosensitization will be selective towards cancer cells.