Document Detail


Cell cycle as a target of antineoplastic drugs.
MedLine Citation:
PMID:  20166983     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell cycle consists of a number of complex biochemical pathways that ensure that the start of a particular event depends on the successful and right end of previous steps in the pathway. An important role is played by cyclin/cyclin-dependent kinase (cdk) complexes which are critical regulators of cell cycle progression and RNA transcription. To ensure proper progression through each phase, cells have developed a series of orchestrated checkpoints that govern the different cellular kinases required for distinct cell cycle events. In particular, several cell cycle protein kinases, including members of the Aurora family and the Polo-like kinases, play critical roles in mitotic entry and chromosome segregation that ensure the correct formation of daughter cells. Tumour cell proliferation is frequently associated to both genetic and epigenetic mechanisms commonly affecting the expression of cell cycle regulatory proteins or causing an incompetent checkpoint control, resulting in aberrant responses to cellular damage. These alterations result not only in proliferative advantages but also in an increased susceptibility to the accumulation of additional genetic alterations that contribute to tumour progression and acquisition of more aggressive phenotypes. In the last years, the identification of anticancer drugs directed against critical cell cycle regulators has received particular attention. Specifically, several preclinical and clinical trials are addressing cdks or cell cycle protein kinase inhibitors. Starting from a description of cell cycle, this review summarizes the most recent studies on drugs targeting cell cycle regulators that are being used in cancer therapy.
Authors:
Maria De Falco; Antonio De Luca
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  16     ISSN:  1873-4286     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2010  
Date Detail:
Created Date:  2010-05-27     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1417-26     Citation Subset:  IM    
Affiliation:
School of Medicine, Second University of Naples Via L. Armanni, 5, 80138 Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology,  therapeutic use*
Cell Cycle / drug effects*
Cell Cycle Proteins / antagonists & inhibitors
Cell Line, Tumor
Clinical Trials as Topic
Humans
Neoplasms / drug therapy*,  enzymology,  pathology
Protein Kinases / metabolism
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cell Cycle Proteins; EC 2.7.-/Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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