Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology

SIMPLE SUMMARY: Heat shock factor 1 (HSF1) is a transcription factor crucial for cellular stress responses. HSF1 activates heat shock proteins (HSPs) in response to proteotoxic stress, aiding in protein folding and maintaining proteostasis. HSF1 is often overexpressed in various cancer cells, fueling malignancy and indicating a poor prognosis. The mechanisms behind HSF1-induced tumorigenesis are complex and cancer type-dependent. Targeting HSF1 presents a novel cancer treatment strategy. ABSTRACT: Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1′s roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.