Combining an Hsp70 inhibitor with either an N- or C-terminal Hsp90 inhibitor produces mechanistically distinct phenotypes.

Abstract

Blocking the function of both heat shock protein 90 and 70 (Hsp90 and Hsp70) simultaneously limits these chaperones' cytoprotective effects on cancer cells. The unique phenotype associated with modulating Hsp90's C-terminus, when used in combination with Hsp70 inhibitors, produces a synergistic and highly relevant dual chemotherapy regimen.