The present invention includes the use of a nucleic acid sequence encoding an shRNA to target RNA interference against a cellular factor where such use can enhance oncolytic adenovius replication. The nucleic acid sequence encoding an shRNA can be introduced into an oncolytic adenovius construct via a recombination event, and such nucleic acid sequence encoding an shRNA can reside in either the E1 region or Fiber region of the oncolytic adenovius construct. In particular, the oncolytic adenovius construct optionally include a prostate specific promoter or prostate specific enhancer for issue specific expression in prostate cancer cells. The oncolytic adenovius constructs of the invention provides utility for the treatment of cancers, in particular prostate cancer.
