Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells.
To address the increased need to understand the similarities and differences in targeting Aurora A or Aurora B for the treatment of cancer, we systematically evaluated the relative importance of Aurora A and/or Aurora B as molecular targets using antisense oligonucleotides. It was found that perturbations in Aurora A and Aurora B signaling result in growth arrest and apoptosis preferentially in cancer cells. The biological fingerprints of Aurora A and Aurora B inhibition were compared and contrasted in efforts to identify the superior therapeutic target. Due to the different biological responses, we conclude that each Aurora kinase should be treated as autonomous drug targets, which can be targeted independently or in combination. We observed no advantages to targeting both kinases simultaneously and feel that an Aurora A-targeted therapy may have some beneficial consequences over an Aurora B-targeted therapy, such as mitotic arrest and the rapid induction of apoptosis.
Warner
Steven L
SL
College of Pharmacy, University of Arizona, Tucson, Arizona, USA.
Munoz
Ruben M
RM
Stafford
Phillip
P
Koller
Erich
E
Hurley
Laurence H
LH
Von Hoff
Daniel D
DD
Han
Haiyong
H
D017209:Apoptosis; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D014410:Tumor Stem Cell Assay
D016376:Oligonucleotides, Antisense; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases