Hsp70 and Hsp27: Emerging targets in cancer therapy

Abstract

Heat shock proteins (Hsps) Hsp27 and Hsp70 are powerful chaperones whose expression is induced in response to a wide variety of physiological and environmental insults including anti-cancer chemotherapy, thus allowing the cell to survive to lethal conditions. Hsp27 and Hsp70 cytoprotective properties may be explained by their anti-apoptotic function. Indeed, both proteins can inhibit key effectors of the apoptotic machinery at the pre- and post-mitochondrial level. In cancer cells, the expression of Hsp27 and/or Hsp70 is abnormally high, and both Hsp27 and Hsp70 may participate in oncogenesis and in resistance to chemotherapy. In rodent models, Hsp27 or Hsp70 overexpression increases tumor growth and metastatic potential. The depletion or inhibition of Hsp27 and Hsp70 frequently reduces the size of the tumors and even can cause their complete involution (for Hsp70). But Hsp27 and Hsp70 can also be found in the extracellular medium. Their role is then immunogenic and the term chaperokine to define the extracellular chaperones has been advanced. Hsps are being used linked to tumor antigens in the development of vaccines. Hsp27 and Hsp70 intracellular and extracellular functions as well as the strategies that are being developed in cancer therapy exploiting these Hsps properties will be comment in this chapter.