Inhibiting the transcription factor HSF1 as an anticancer strategy

Abstract

Background: In mammals, the cytoprotective heat-shock response is regulated primarily by heat shock factor 1 (HSF1). Unfortunately, the effects of HSF1 also support the ability of cancer cells to accommodate imbalances in signaling and alterations in DNA, protein and energy metabolism associated with oncogenesis. The malignant lifestyle confers dependence on this ‘non-oncogene’, suggesting a therapeutic role for HSF1 inhibitors. Objective/methods: We begin with an overview of how HSF1 affects cancer biology and how its activity is regulated. We then summarize progress in discovery and development of HSF1 inhibitors, their current limitations and potential as anticancer agents with a fundamentally different scope of action from other clinically validated modulators of protein homeostasis. Results/conclusions: It is likely that within the next 5 years usable inhibitors of HSF1 will be identified and in early pre-clinical evaluation.