Target validation and biomarker identification in oncology : the example of aurora kinases.
The strong link between gene expression of mitotic Aurora kinases and cancer has stimulated a very high interest in developing Aurora kinase inhibitors for cancer therapy. Validation of Aurora kinases as targets, and development of pharmacodynamic biomarkers for inhibitors of Aurora kinases, provides an example of how target validation can help the drug discovery process, and also of how to interpret results depending on the technology used. In this review, we outline the principal tools, concepts, and strategies of target and biomarker validation for Aurora kinases, with emphasis on validation results derived from RNA-interference experiments. These data were essential for the decision to enter the next steps in drug development and for the selection of the appropriate biomarkers for clinical trials.
Colombo
Riccardo
R
Nerviano Medical Sciences Srl, Nerviano, Italy.
Moll
Jürgen
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000302:isolation & purification; D016503:Drug Delivery Systems; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D054928:Validation Studies as Topic
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases