# PLK4

Source: https://onco.cc/targets/plk4/  
OnCo record `plk4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

PLK4 is the enzyme that starts the copying of the centrosome, the structure that organises a dividing cell's spindle. Cancers with extra copies of the TRIM37 gene cannot divide properly once PLK4 is blocked, and two PLK4 inhibitors are in early trials.

## Summary

PLK4 (chromosome 4q28.1) is a serine/threonine kinase with a central role in centriole duplication: it triggers the formation of a new centriole on the parent one, and when overexpressed it can drive centrosome amplification (UniProt O00444). A 2020 Nature study found that after PLK4 inhibition cells divide without centrosomes, and that high levels of the ubiquitin ligase TRIM37 stop this centrosome-free spindle assembly, causing mitotic failure; the TRIM37 region on chromosome 17q is frequently amplified in neuroblastoma and breast cancer, which made those cancers highly sensitive to PLK4 inhibition in that work (Meitinger et al.,doi:10.1038/s41586-020-2710-1). In OnCo, CFI-400945 is tested in myeloid cancers and breast cancer, and RP-1664 is described by its developer as a synthetic-lethal PLK4 inhibitor linked to TRIM37 overexpression.

## Fields

- Kind: Target
- Last checked: 2026-11-03
- Also known as: polo like kinase 4; polo-like kinase 4; STK18
- Tags: pipeline-gap-target
- Symbol: PLK4
- Class: kinase
- Biology: Kinase that initiates procentriole formation on the parental centriole and recruits centriole-building proteins such as SASS6 and CPAP; overexpression produces multiple procentrioles per parent centriole (UniProt O00444).
- Where found: Cancers with TRIM37 (chromosome 17q) gain, including neuroblastoma and breast cancer, in preclinical work (doi:10.1038/s41586-020-2710-1); Myeloid cancers and breast cancer (CFI-400945 trials)

## Notes

- Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate.

## Sources

- HGNC HGNC:11397: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11397
- UniProt O00444: https://www.uniprot.org/uniprotkb/O00444/entry
- NCBI Gene 10733: https://www.ncbi.nlm.nih.gov/gene/10733
- TRIM37 controls cancer-specific vulnerability to PLK4 inhibition (Nature 2020): https://doi.org/10.1038/s41586-020-2710-1

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/)
- drugs: [CFI-400945](https://onco.cc/drugs/cfi-400945/), [RP-1664](https://onco.cc/drugs/rp-1664/)

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JSON: https://onco.cc/api/v1/entities/plk4.json