The heat shock proteins as targets for radiosensitization and chemosensitization in cancer

Abstract

The heat shock proteins (HSPs) represent a class of proteins which are induced under physiologic stress to promote cell survival in the face of endogenous or exogenous injury. HSPs function predominantly as molecular chaperones, maintaining their "client" proteins in the correct conformational state in order to withstand a biologic stressor. Elevated HSP expression is also found in a range of pathologic conditions, notably malignancy. Cancer cells exploit the pro-survival phenotype endowed by HSPs to bolster their proliferative potential. Consequently, developing means of abrogating HSP expression may provide a way to render cancer cells more susceptible to radiation or chemotherapy. Here, we review the members of the HSP class and their roles in malignancy. We focus on attempts to target these proteins, particularly the small HSPs, in developing potent radiation and chemotherapy sensitizers, as well as proposed mechanisms for this sensitization effect.

Figure 1

Proposed mechanisms of action for HSP inhibitors in radiosensitization and chemosensitization.