Klin Padiatr 2022; 234(03): 184
DOI: 10.1055/s-0042-1748722
Abstracts

Epigenetic perturbation by BMI-1 inhibitors as a novel therapeutic approach for hepatoblastoma

S Demir
1   Department of Pediatric Surgery, Dr. von Hauner Children’s Hospital, LMU Munich, Germany
,
M Bentrop
1   Department of Pediatric Surgery, Dr. von Hauner Children’s Hospital, LMU Munich, Germany
,
S Cairo
2   XenTech, Evry, France
,
R Kappler
1   Department of Pediatric Surgery, Dr. von Hauner Children’s Hospital, LMU Munich, Germany
› Author Affiliations
 

Treatment of hepatoblastoma (HB) has drastically improved by refinements of surgical procedures and clinical risk stratification. However, identifying novel drug and molecular targets is still crucial due to the resistance towards conventional chemotherapy and its toxicity. Since the mutational frequency is extremely low in HB, targeting strategies based on genetic alterations is challenging, addressing the involvement of epigenetic modifications. In this project, we tested 11 compounds directed against epigenetic regulators on 10 HB cell lines and compared their efficacy to standard of care chemotherapeutics. Consequent viability assays revealed that the polycomb complex protein BMI-1 inhibitors PTC209 and PTC596 reduced HB cell growth in a dose-dependent manner. Moreover, reduction of colony formation capability, decrease of migration potential, induction of apoptotis, retardation of proliferation and 3-dimensional spheroid growth were observed in HB cells upon BMI-1 inhibition. Furthermore, the combination of BMI-1 inhibitors and cisplatin revealed a strong synergistic effect, suggesting BMI-1 inhibition as a potential target for HB therapy.



Publication History

Article published online:
17 May 2022

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