FICAN Science Webinar ”De novo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatment options”
Published 27.1.2026
FICAN Science Webinars are nationwide events that provide a platform for sharing new scientific findings, highlighting recent advances in cancer research, and fostering collaboration between cancer researchers and clinicians across Finland. The webinar is open for all interested in cancer research.
11.02 @ 15:00 – 16:00
Speaker: Professori Riikka Kivelä, University of Jyväskylä
Get to know to the speaker: Riikka Kivelä | Jyväskylän yliopisto
Topic: De novo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatment options
This session is hosted by FICAN East. The webinar will be held online (via Microsoft Teams): Join the meeting here
Abstract
Rhabdomyosarcoma (RMS) is an aggressive pediatric soft-tissue cancer. Identification of RMS precursor cells and models has been a challenge due to unknown molecular mechanisms that drive the common proliferative myogenic phenotype. Our studies have revealed that the PROX1 transcription factor is essential for the growth and myogenic features of RMS, and its downregulation reverts RD cells to a phenotype resembling benign mesenchymal stem cells. Our findings demonstrate that the effects of PROX1 on RMS cell growth are mediated by FGFR, predominantly by FGFR1 and FGFR4, which were found to compensate for each other. Our findings place PROX1 as a major mediator of RMS characteristics and development and suggests that pan-FGFR inhibitors provide a promising option for the treatment of RMS. We have also identified de novo cholesterol biosynthesis as a key metabolic vulnerability in rhabdomyosarcoma, regulated by PROX1. Cholesterol synthesis inhibition halts RMS cell proliferation and triggers ER stress-induced apoptosis, offering a promising therapeutic strategy. The findings highlight a potential therapeutic strategy for rhabdomyosarcoma by targeting de novo cholesterol biosynthesis, as statins are already widely used and well tolerated.
Relevat references from the speaker for this talk:
Gizaw NY, Kallio P, Punger T, Gucciardo E, Haglund C, Böhling T, Lehti K, Sampo M, Alitalo K, Kivelä R. PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2116220119. doi: 10.1073/pnas.2116220119.
Gizaw NY, Kolari K, Kallio P, Alitalo K, Kivelä R. Inhibiting cholesterol synthesis halts rhabdomyosarcoma growth via ER stress and cell cycle arrest. EMBO Mol Med. 2025 Dec;17(12):3586-3606. doi: 10.1038/s44321-025-00336-x.
