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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.
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.
In plain words · 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.
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.
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).
2 products aim at PLK4: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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).
CFI-400945 is an experimental small molecule from Treadwell Therapeutics, in phase 2 trials for acute myeloid leukaemia, myelodysplastic syndromes and chronic myelomonocytic leukaemia and other cancers.
RP-1664 is an experimental oral small molecule kinase inhibitor from Repare Therapeutics, in phase 1 trials for advanced solid tumours, with and without TRIM37 amplification; its current status is not stated.
Query for this target: (TITLE:"PLK4" OR ABSTRACT:"PLK4" OR TITLE:"polo like kinase 4" OR ABSTRACT:"polo like kinase 4" OR TITLE:"polo-like kinase 4" OR ABSTRACT:"polo-like kinase 4" OR TITLE:"STK18" OR ABSTRACT:"STK18") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PLK4, not a curated reading list.
Shares Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia and the tag pipeline-gap-target.
Shares Acute myeloid leukaemia and the tag pipeline-gap-target.
Shares Breast cancer (all types) and the tag pipeline-gap-target.
Shares Acute myeloid leukaemia and the tag pipeline-gap-target.
Shares CFI-400945, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares CFI-400945, Breast cancer (all types).
Shares CFI-400945, Breast cancer (all types).
Shares Neuroblastoma (paediatric), Acute myeloid leukaemia, Breast cancer (all types).
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