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Effect of RM-006 treatment on gene expression in LN229 cells

ABSTRACT: Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common feature of cancer but, while mTOR kinase represents an attractive drug target, mTOR inhibitors have not seen broad success as single agents. To identify strategies to enhance the utility of mTOR inhibitors we performed forward genetic screens with new bi-steric mTORC1 inhibitors. These screens show that mTORC1 inhibitor-mediated cytostasis leaves cells exquisitely dependent on the lipid peroxide scavenging enzyme GPX4. Mechanistically, using unbiased gene activation screens and RNA-seq, we demonstrate that mTORC1-dependent control of ferroptosis occurs, in part, through regulation of SCARB1 expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE320384 | GEO | 2026/04/16

REPOSITORIES: GEO

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CRISPRi/a screens to identify modifiers of response to the bi-steric mTORC1 inhibitor RM-006

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CRISPRi/a screens to identify modifiers of response to the bi-steric mTORC1 inhibitor RM-006

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