{"entity":{"id":"plk4","kind":"target","name":"PLK4","aka":["polo like kinase 4","polo-like kinase 4","STK18"],"tldr":"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.","asOf":"2026-11-03","links":[{"label":"HGNC HGNC:11397","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11397"},{"label":"UniProt O00444","url":"https://www.uniprot.org/uniprotkb/O00444/entry"},{"label":"NCBI Gene 10733","url":"https://www.ncbi.nlm.nih.gov/gene/10733"},{"label":"TRIM37 controls cancer-specific vulnerability to PLK4 inhibition (Nature 2020)","url":"https://doi.org/10.1038/s41586-020-2710-1"}],"tags":["pipeline-gap-target"],"related":[],"cancers":["neuroblastoma","breast-cancer","aml","mds"],"sections":[],"technologies":[],"targets":[],"drugs":["cfi-400945","rp-1664"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate."],"provenance":{"editedBy":"OnCo gap audit, class 5 targets (HGNC REST, UniProt REST, Europe PMC, corpus drug records)","editedOn":"2026-11-03"},"symbol":"PLK4","role":["drug-target"],"sources":[],"specificitySources":[],"hgnc":"HGNC:11397","ensembl":"ENSG00000142731","uniprot":"O00444","entrez":"10733","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).","whereFound":["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)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/plk4/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"}],"drug":[{"id":"cfi-400945","kind":"drug","name":"CFI-400945","route":"/drugs/cfi-400945/"},{"id":"rp-1664","kind":"drug","name":"RP-1664","route":"/drugs/rp-1664/"}]}}