CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent kinase, CDK1. This was discovered using parallel siRNA screens in KRAS mutant...

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Veröffentlicht in:	PloS one 2016-02, Vol.11 (2), p.e0149099
Hauptverfasser:	Costa-Cabral, Sara, Brough, Rachel, Konde, Asha, Aarts, Marieke, Campbell, James, Marinari, Eliana, Riffell, Jenna, Bardelli, Alberto, Torrance, Christopher, Lord, Christopher J, Ashworth, Alan
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Amino acids Analysis Animals Antineoplastic Agents - pharmacology Biology and life sciences Breast cancer Causes of CDC2 Protein Kinase Cell culture Cell cycle Cell Line, Tumor Colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Cyclin-dependent kinases Cyclin-Dependent Kinases - antagonists & inhibitors Cyclin-Dependent Kinases - genetics Cyclin-Dependent Kinases - metabolism Dose-Response Relationship, Drug Female G1 Phase Cell Cycle Checkpoints - drug effects Gene Expression Regulation, Neoplastic Gene mutation Genes Genes, Lethal Genetic aspects Genetic screening High-Throughput Screening Assays Humans Imidazoles - pharmacology K-Ras protein Kinases Laboratories Lethality Medical research Medicine and Health Sciences Mice Mice, Inbred BALB C Mice, Nude Mutation Pancreas Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Physiological aspects Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism Pyrimidines - pharmacology Quinolines - pharmacology Ras genes Research parks RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction siRNA Survival Analysis Thiazoles - pharmacology Tumors Xenograft Model Antitumor Assays Xenografts
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