Antisense oligonucleotides directed to genes regulated by trapoxin-induced HDAC inhibition

摘要

Antisense compounds, compositions and methods are provided for modulating the expression of trapoxin A regulated genes, including but not limited to those genes induced by ectopic expression of p21^waf1 that are disclosed herein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding these genes. Methods of using these compounds for modulation of expression of these genes and for treatment of diseases associated with these genes, as well as those associated with abnormal HDAC activity, particularly cancer or others characterized by abnormal cell proliferation, are provided. Furthermore, the invention relates to the use of RhoB as a biomarker to evaluate the efficacy of treatment of humans with abnormal HDAC activity including proliferative diseases such as cancer. Also disclosed is a method for identifying HDAC inhibitors and trapoxin analogs based on the surprising discovery that up regulation or RhoB and increased RhoB protein levels are associated with HDAC inhibition.