Dual inhibition of HSF1 and DYRK2 impedes cancer progression

Vasudha Tandon, Rita Moreno, Kira Allmeroth, Jean Quinn, Sandra E. Wiley, Lynden G. Nicely, Martin S. Denzel, Joanne Edwards, Laureano de la Vega, Sourav Banerjee (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
60 Downloads (Pure)


Preserving proteostasis is a major survival mechanism for cancer. DYRK2 is a key oncogenic kinase that directly activates the transcription factor HSF1 and the 26S proteasome. Targeting DYRK2 has proven to be a tractable strategy to target cancers sensitive to proteotoxic stress, however, the development of HSF1 inhibitors remains in its infancy. Importantly, multiple other kinases have been shown to redundantly activate HSF1 which promoted ideas to directly target HSF1. The eventual development of direct HSF1 inhibitor KRIBB11 suggests that the transcription factor is indeed a druggable target. The current study establishes that concurrent targeting of HSF1 and DYRK2 can indeed impede cancer by inducing apoptosis faster than individual targetting. Furthermore, targeting the DYRK2-HSF1 axis induces death in proteasome inhibitor resistant cells and reduces triple-negative breast cancer burden in ectopic and orthotopic xenograft models. Together the data indicate that co-targeting of kinase DYRK2 and its substrate HSF1 could prove to be a beneficial strategy in perturbing neoplastic malignancies.

Original languageEnglish
Article numberBSR20222102
Number of pages14
JournalBioscience Reports
Issue number1
Early online date30 Jan 2023
Publication statusPublished - Jan 2023


  • stress kinases
  • inhibition
  • myeloma
  • proteasomes

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology


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