Histone H3 K27M mediated regulation of cancer cell stemness and differentiation in DIPG

Abstract - 3965 / 10 - Histone H3 K27M mediated regulation of cancer cell stemness and differentiation in diffuse intrinsic pontine glioma (DIPG)

AACR; 2022 - April 13, 2022, 9:00 AM - 12:30 PM

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https://www.abstractsonline.com/pp8/#!/10517/presentation/16072

"In addition, DNA repair, along with PI3K/AKT and Wnt signaling, were found to be upregulated upon radiation of DIPG cells, indicating future therapeutic opportunities to prevent radio resistance. We have co-targeted these cell-intrinsic vulnerabilities to eradicate CSCs in DIPG and prevent tumor recurrence, using a combination of radiotherapy, the PI3K/mTOR inhibitor GDC-0084 and the ALDH inhibitor Disulfiram. This combination has produced an exquisite synergy in cells, which we will test in clinically-relevant DIPG models. Taken together, through these studies we have gained mechanistic insight into H3K27M mediated regulation of cancer cell stemness and differentiation in DIPG, which appears to be mediated by Wnt-dependent signaling of ALDH1A3 and provides rationale for exploring new therapeutic targets".

Matt Dun's publication for DIPG research, with the combination of paxalisib and ONC201 is still eagerly awaited!

Regards.