The Hsp70 Family of Heat Shock Proteins in Tumorigenesis: From Molecular Mechanisms to Therapeutic Opportunities

The HSP70 family of molecular chaperones consists of at least eight members that are highly evolutionarily conserved. Whereas more than one member of this family is implicated in cancer, the most compelling and abundant data point to the involvement of the predominant stress-inducible form of this protein in cancer etiology and progression. High levels of HSP70 staining in tumors emerged as a significant marker of poor prognosis in human tumors over 20 years ago. Since that time, the important role of this protein in cellular transformation, viral infection, immune function, and the cellular stress response has come to be appreciated and understood. In the past 10 years, the findings that many different types of human tumors are addicted to this protein for survival, and that silencing HSP70 is cytotoxic to tumor but not normal cells, have led to the emergence of the first specific inhibitors of this family of molecular chaperones for cancer therapy. Here-in we review the pro-tumorigenic function(s) of this protein, our understanding of how HSP70 mediates protein quality control, and the current efforts to target and inhibit this protein for cancer therapy.