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- W2320221618 abstract "C130 Polo-like kinases (PLK) are a family of serine threonine kinases that are critical regulators of cell cycle progression, mitosis, cytokinesis and DNA damage response. Elevated expression of PLK1 has been observed in many types of cancer and is associated with poor outcome in some cases. PLK1, therefore, has been proposed to be target for cancer therapy. GSK461364 is a small molecule that has been developed to selectively inhibit PLK1. Predictive biomarkers may allow stratification of patients and potentially increase response rates in clinical trials. Based upon cancer cell line sensitivity data measured by a drug washout assay, it was found that mutations in the TP53 gene are associated with sensitivity to GSK461364. Genome wide copy number analysis, derived from Affymetrix 500k ‘SNP chip’, indicates that the GSK461364 sensitive lines harbor more overall chromosome instability (CIN) that is represented by the accumulation of DNA copy number changes. PLK1 has been shown to regulate both the activity and stability of the p53 protein, and others have shown that siRNA knockdown of PLK1 preferentially reduced the survival of p53 defective cancer cells. PLK1 and TP53 are both critical players in the G2/M checkpoint, where disruption can result in CIN. It has also been reported that loss of p53 function can cause CIN, thus strengthening the notion that either TP53 sequence status or CIN status can be used as potential predictive biomarkers for response to GSK461364." @default.
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- W2320221618 date "2007-11-01" @default.
- W2320221618 modified "2023-09-27" @default.
- W2320221618 title "Association of mutations in the TP53 gene and chromosome instability with sensitivity to the PLK1 inhibitor GSK461364" @default.
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