HSP70 AND HSP27 AS PHARMACOLOGICAL TARGETS IN APOPTOSIS MODULATION FOR CANCER THERAPY Heat shock proteins and Cancer

The expression of heat shock proteins (HSP) HSP70 and HSP27 is induced in response to a wide variety of physiological and environmental insults including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. The cytoprotective effect of HSP70 and HSP27 is related to their ability to disable apoptosis. HSP70 and HSP27 both inhibit key apoptotic proteins at the pre- and post-mitochondrial level. HSP70 and/or HSP27 basal levels are unusually high in malignant cells, and both have been accused of participating in oncogenesis and/or in chemotherapy resistance. In rodent models, HSP70 or HSP27 over-expression increases tumor growth and metastatic potential. HSP70 and HSP27 depletion or inhibition frequently reduces the size of the tumors and even can cause their complete involution (for HSP70). In this chapter we will describe the effectors of the apoptotic machinery that interact with HSP70 or HSP27, and we will discuss the inhibition of HSP70 and HSP27 as a novel strategy of cancer therapy