Edward Hurley, MD., Assistant professor in the department of Pediatrics, Associate member of the PLRC and 2022 Pilot & Feasibility grant awardee published an article in the Journal of Pathology entitled: “Inhibition of HSF1 Signaling Decreases Hepatoblastoma Growth Via Induction of Apoptosis”. The study was done in collaboration with PLRC members Silvia Liu and Paul Monga. https://doi.org/10.1016/j.ajpath.2022.10.006
Abstract:
Although rare compared with adult liver cancers, hepatoblastoma (HB) is the most common pediatric liver malignancy, and its incidence is increasing. Treatment currently includes surgical resection with or without chemotherapy, but in severe cases children require liver transplantation. The effort to develop more targeted, HB-specific therapies has been stymied by the lack of fundamental knowledge about the HB biology. Heat shock factor 1 (HSF1) is a transcription factor that is a canonical inducer of heat shock proteins, which act as chaperone proteins to prevent or undue protein misfolding. Recent work has shown a role for HSF1 in cancer beyond the canonical heat shock response. We found increased HSF1 signaling in HB versus normal liver. We also found that less differentiated, more embryonic tumors had higher levels of HSF1 than more differentiated, more fetal-appearing tumors. Most strikingly, we found HSF1 expression levels correlated with mortality. Our laboratory has discovered a method to make HB-like disease develop in mice. We used this model to test how inhibiting HSF1 early in tumor development would impact cancer growth. We found fewer and smaller tumors when HSF1 was inhibited, suggesting HSF1 is needed for aggressive tumor growth. Moreover, increased apoptosis in tumor foci was noted when HSF1 was inhibited. These data suggest HSF1 may be a viable pharmacologic target for HB treatment.
Hurley EH, Tao J, Liu S, Krutsenko Y, Singh S, Monga SP. Inhibition of Heat Shock Factor 1 Signaling Decreases Hepatoblastoma Growth via Induction of Apoptosis. Am J Pathol. 2022 Nov 3:S0002-9440(22)00355-8. doi: 10.1016/j.ajpath.2022.10.006. Epub ahead of print. PMID: 36336065.
