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Editorial
. 2022 Mar;26(3):187-192.
doi: 10.1080/14728222.2022.2040017. Epub 2022 Feb 10.

Atypical teratoid rhabdoid tumor (ATRT): disease mechanisms and potential drug targets

Julian S Rechberger  1   2 , Cody L Nesvick  2 , David J Daniels  2
Affiliations
Editorial

Atypical teratoid rhabdoid tumor (ATRT): disease mechanisms and potential drug targets

Julian S Rechberger et al. Expert Opin Ther Targets. 2022 Mar.
No abstract available

Keywords: ATRT; Atypical teratoid rhabdoid tumor; BAF; SMARCB1; SWI/SNF; enhancer; epigenomics; rhabdoid tumor; targeted therapeutics.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Basic BAF complex composition and epigenetic function. The canonical SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex (canonical BAF [cBAF] complex) is a multi-subunit modulator of gene transcription implicated in vital cellular functions such as cell differentiation, lineage determination, and self-renewal. In the absence of a functional SMARCB1 subunit, less BAF complex is recruited to typical enhancers, which is accompanied by loss of histone acetylase activity and deranged polycomb-signaling at these sites of transcriptional regulation. Super enhancer activity is selectively retained at genes that contribute to immortality and cell proliferation in the absence a functional SMARCB1 subunit (created with BioRender.com).
Figure 2.
Figure 2.
Summary of potential therapeutic strategies. Groundbreaking findings in the fields of BAF and enhancer biology have revealed a central role for epigenetic dysregulation in the pathogenesis of ATRT. A variety of different therapies targeting secondary epigenetic vulnerabilities are currently being investigated in preclinical studies and clinical trials. Among others, these pathophysiologically relevant and potentially subgroup-specific therapeutic approaches include inhibition of AURK, CDK4/6, MYC, and polycomb, which may be therapeutically targeted by alisertib, ribociclib, dasatinib, tazemetostat, respectively. An alternative strategy is to target residual BAF, and a few select compounds (e.g. FHD-609 and FHD-286) are likewise in clinical trial for cancers that contain a mutation in a BAF complex subunit (created with BioRender.com).
See this image and copyright information in PMC

References

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