Are some Hsp90 therapies more effective than others? Evaluating dual Hsp90 and Hsp70 inhibition as an anticancer therapy

The heat shock proteins (Hsps) are a family of highly conserved proteins involved in the regulation of numerous cellular processes including those associated with cancer. Inhibiting the function of these Hsps, specifically Hsp70 and Hsp90, is a major strategy used in the development of new cancer therapies. Numerous Hsp90 inhibitors have been evaluated in the clinic, and while some have experienced success, many have produced disappointing results. One reason explaining their failure is that they induce a cytoprotective response that protects cancer cells from the negative effects of Hsp90 inhibition. In order to maximise the therapeutic outcomes, dual inhibition of Hsp70 and Hsp90 can be employed to overcome cell rescue mechanisms induced by monotherapies. In this chapter, we discuss dual inhibition of Hsp70 and Hsp90 using small molecules and evaluate the potential of this strategy for the development of cancer therapeutics