HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms

Front Cell Dev Biol. 2025 Jan 9:12:1500880. doi: 10.3389/fcell.2024.1500880. eCollection 2024.

Abstract

Heat Shock Factor 1 (HSF1) is a major transcriptional factor regulating the heat shock response and has become a potential target for overcoming cancer chemoresistance. This review comprehensively examines HSF1's role in chemoresistance and its potential as a therapeutic target in cancer. We explore the complex, intricate mechanism that regulates the activation of HSF1, HSF1's function in promoting resistance to chemotherapy, and the strategies used to manipulate HSF1 for therapeutic benefit. In addition, we discuss emerging research implicating HSF1's roles in autophagy, apoptosis, DNA damage repair, drug efflux, and thus chemoresistance. This article highlights the significance of HSF1 in cancer chemoresistance and its potential as a target for enhancing cancer treatment efficacy.

Keywords: apoptosis; autophagy; chemoresistance; drug efflux; heat shock factor 1; proteotoxic stress response.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the University of Toledo Fund Number #110917 and the National Cancer Institute of the National Institutes of Health under Award Number K22CA248616. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.