What question did this study set out to answer?

The study aims to identify effective combination therapies for RAS-driven multiple myeloma by exploring genetic vulnerabilities.

Abstract A018: Functional chemo-genomic screening identifies novel combination therapies to treat RAS-driven multiple myeloma

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Functional screening identifies synergistic therapies in RAS-driven multiple myeloma, suggesting new treatment avenues.

The study aims to identify effective combination therapies for RAS-driven multiple myeloma by exploring genetic vulnerabilities.
Integrated whole-genome CRISPR screens with high-throughput chemogenomic profiling in multiple myeloma cell lines.
Evaluated the pan-RAS inhibitor RMC-6236 against a library of nearly 3000 small molecules.
Conducted phosphoproteomic profiling to assess signaling pathways affected by treatment.
Performed in vivo validation using KRAS- and NRAS-driven multiple myeloma xenografts.
RMC-6236 showed low-nanomolar activity across diverse multiple myeloma cell lines, particularly those dependent on RAS and FGFR3.
Identified the SWI/SNF inhibitor FHD-286 as a strong synergistic partner in combination therapies.
Phosphoproteomic profiling indicated robust suppression of MAPK and mTORC1 signaling pathways.
In vivo studies revealed rapid tumor regression in KRAS- and NRAS-driven xenografts with minimal toxicity.

Al‐Odat et al. (2026) studied this question.

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