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10.1038/nrd4504 http://scihub22266oqcxt.onion/10.1038/nrd4504 C4480421!4480421!25633797     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Rev+Drug+Discov 2015 ; 14 (2): 130-46 Nephropedia Template TP {{tp|p=25633797|t=2015. The history and future of targeting cyclin-dependent kinases in cancer therapy |pdf=|usr=}}{{25633797}} gab.com Text The history and future of targeting cyclin-dependent kinases in cancer therapy JO: Nat Rev Drug Discov http://www.kidney.de/pget.php?&tw=1&pmid=25633797 #FOAvip Cancer represents a pathological manifestation of uncontrolled cell division; therefore, it has long been anticipated that our understanding of the basic principles of cell cycle control would result in effective cancer therapies. In particular, cyclin-dependent kinases (CDKs) that promote transition through the cell cycle were expected to be key therapeutic targets because many tumorigenic events ultimately drive proliferation by impinging on CDK4 or CDK6 complexes in the G1 phase of the cell cycle. Moreover, perturbations in chromosomal stability and aspects of S phase and G2/M control mediated by CDK2 and CDK1 are pivotal tumorigenic events. Translating this knowledge into successful clinical development of CDK inhibitors has historically been challenging, and numerous CDK inhibitors have demonstrated disappointing results in clinical trials. Here, we review the biology of CDKs, the rationale for therapeutically targeting discrete kinase complexes and historical clinical results of CDK inhibitors. We also discuss how CDK inhibitors with high selectivity (particularly for both CDK4 and CDK6), in combination with patient stratification, have resulted in more substantial clinical activity. Twit Text FOAVip The history and future of targeting cyclin-dependent kinases in cancer therapy ????Nat Rev Drug Discov http://www.kidney.de/pget.php?&tw=1&pmid=25633797 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25633797 #FOAvip English Wikipedia <ref>{{Cite pmid|25633797}}</ref> The history and future of targeting cyclin-dependent kinases in cancer therapy #MMPMID25633797 Asghar U; Witkiewicz AK; Turner NC; Knudsen ES Nat Rev Drug Discov 2015[Feb]; 14 (2): 130-46 PMID25633797show ga Cancer represents a pathological manifestation of uncontrolled cell division; therefore, it has long been anticipated that our understanding of the basic principles of cell cycle control would result in effective cancer therapies. In particular, cyclin-dependent kinases (CDKs) that promote transition through the cell cycle were expected to be key therapeutic targets because many tumorigenic events ultimately drive proliferation by impinging on CDK4 or CDK6 complexes in the G1 phase of the cell cycle. Moreover, perturbations in chromosomal stability and aspects of S phase and G2/M control mediated by CDK2 and CDK1 are pivotal tumorigenic events. Translating this knowledge into successful clinical development of CDK inhibitors has historically been challenging, and numerous CDK inhibitors have demonstrated disappointing results in clinical trials. Here, we review the biology of CDKs, the rationale for therapeutically targeting discrete kinase complexes and historical clinical results of CDK inhibitors. We also discuss how CDK inhibitors with high selectivity (particularly for both CDK4 and CDK6), in combination with patient stratification, have resulted in more substantial clinical activity. äThe history and future of targeting cyclin-dependent kinases in cancer(epmc).pdf DeepDyve Pubget Overpricing