Genomics

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CDK7 Inhibition Suppresses Melanoma Growth By Depleting A Super-enhancer Associated "Achilles" Lineage Cluster [ChIP-Seq]


ABSTRACT: Cutaneous malignant melanoma (CMM) lacks targeted therapies beyond the oft-circumvented BRAF inhibitors. Part of the difficulty in treating melanomas has been attributed to a strong survival program controlled by melanocyte transcription factors such as MITF - a phenomenon first described in melanoma as “lineage dependency.” Recently, a highly selective covalent CDK7 inhibitor (THZ1) has been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We now show that melanoma cells are highly sensitive to CDK7 inhibition and that a melanocyte “lineage cluster,” whose members are transcriptionally driven by super-enhancers, is also strongly suppressed by THZ1. These results point to CDK7 inhibition as a viable strategy to deprive oncogenic transcription and suppress tumor growth in melanoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75814 | GEO | 2017/10/23

SECONDARY ACCESSION(S): PRJNA305433

REPOSITORIES: GEO

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