
H3-K27M 교모세포종에서 히스톤 디아세틸라제와 MYC 신호 경로를 동시에 억제하면 주요 종양 유발 경로를 효과적으로 차단할 수 있다.


coremsg

Diffuse midline gliomas (DMG) are aggressive and fatal pediatric tumors of the central nervous system that are highly resistant to treatments. Lysine to methionine substitution of residue 27 on histone H3 (H3-K27M) is a driver mutation in DMGs, reshaping the epigenetic landscape of these cells to promote tumorigenesis. H3-K27M gliomas are characterized by deregulation of histone acetylation and methylation pathways, as well as the oncogenic MYC pathway. In search of effective treatment, we examined the therapeutic potential of dual targeting of histone deacetylases (HDACs) and MYC in these tumors. Treatment of H3-K27M patient-derived cells with Sulfopin, an inhibitor shown to block MYC-driven tumors in-vivo , in combination with the HDAC inhibitor Vorinostat, resulted in substantial decrease in cell viability. Moreover, transcriptome and epigenome profiling revealed synergistic effect of this drug combination in downregulation of prominent oncogenic pathways such as mTOR. Finally, in-vivo studies of patient-derived orthotopic xenograft models showed significant tumor growth reduction in mice treated with the drug combination. These results highlight the combined treatment with PIN1 and HDAC inhibitors as a promising therapeutic approach for these aggressive tumors.

### Competing Interest Statement

N.L. is an inventor on a patent describing Sulfopin (US 2021/0332024 A1).

Dual Targeting of Histone Deacetylases and MYC as Potential Treatment Strategy for H3-K27M Pediatric Gliomas

h3-k27m-소아-교모세포종에-대한-히스톤-디아세틸라제와-myc의-이중-표적화가-잠재적-치료-전략이-될-수-있음


H3-K27M 소아 교모세포종에 대한 히스톤 디아세틸라제와 MYC의 이중 표적화가 잠재적 치료 전략이 될 수 있음
