Nature Communications, Published online: 13 June 2026; doi:10.1038/s41467-026-74061-5 Inhibition of PLK4 is synthetic lethal in cancers with chromosome 17q TRIM37 copy number gain. Here, the authors show that while RP-1664 (PLK4 inhibitor) causes centrosome depletion in a TRIM37-dependent manner as high doses, low dose causes cell death in a TRIM37-independent manner via centrosome amplification and demonstrate its efficacy in preclinical models of neuroblastoma with TRIM37 gain.
The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity
John M. Maris