The demonstration that Smad7 antisense oligonucleotide activates PKR and interferes with intracellular pathways that sustain CRC cell survival is consistent with previous studies showing that the activity against CRC of other anti-neoplastic drugs (e.g. non-steroidal anti-inflammatory drug) relies in part on PKR activation.24 PKR is activated by several distinct stress signals or cellular factors.25, 26 Therefore, we next evaluated the factors/mechanisms involved in PKR activation following transfection of CRC cells with Smad7 antisense oligonucleotide. Here, SMAD7 is linked to colorectal carcinoma.