Targets for cancer therapy in the cell cycle pathway.
Progression through the cell cycle is a complex process that is regulated at many levels by several proteins. We are just beginning to understand how these proteins accomplish this regulation. The p16-cyclin D1.cdk4-pRb pathway is one of the most important pathways, which is altered in a majority of cancers of different types. This review focuses on some of the proteins in this pathway that offer new opportunities for drug discovery. Some guidelines to evaluate the relevance of these proteins as targets for cancer therapy and the importance of developing a combination therapy targeting multiple pathways are also discussed.
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Division of Cancer Research, Lilly Research Laboratories, Indianapolis, IN 46285-0424, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015195:Drug Design; D016161:Genes, Retinoblastoma; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D015843:Serpins / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects; D020687:cdc25 Phosphatases
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D015843:Serpins; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex