Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells

Medically Accurate White Blood Cells Attacking Cancer Cell — Scientists have uncovered a new way to reprogram cancer cells by targeting a key protein-making enzyme, which disrupts tumor growth and opens a path to more precise treatments. Credit: Shutterstock

A new study reveals that blocking ribosomal

The discovery shows that the production of ribosomal RNA (rRNA) is connected to how cells manage RNA splicing (a process that edits RNA). In studies of cancer cell lines using drugs that block rRNA production, a new stress response pathway was revealed. This pathway involves proteins called RPL22, RPL22L1, and MDM4. RPL22 plays a key role in controlling RNA splicing in coordination with rRNA production. Credit: Cell Chemical Biology

In their most recent study, the team examined more than 300 cancer cell lines and found that tumors with mutations in the gene RPL22, or with elevated levels of MDM4 and RPL22L1, were especially responsive to Pol 1 inhibitors like BMH-21 and a newly developed drug called BOB-42. These genetic changes are frequently found in cancers with mismatch repair deficiency, or MMRd, including colorectal, stomach, and uterine cancers. MMRd allows copying errors in DOI: 10.1016/j.chembiol.2025.05.012

The research was funded by grants from the National Institutes of Health (R01 GM121404 and P30 CA006973), the National Cancer Institute (K99 CA279786), Blue One Biosciences LLC, Commonwealth Foundation, Mary Kay Ash Charitable Foundation, Academy of Finland (288364), Maryland Cigarette Restitution Fund, and Harrington Scholar-Q9 Innovator Award.

Laiho holds patents on RNA polymerase 1 inhibitors, which are managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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