We provide evidence for an alternative intrinsic pathway/network involving Par-4 partnering with NFκB in the cytoplasm, disruption of DROSHA gene transcription, dysregulation of microRNAs leading to up-regulation of pro-apoptotic and down-regulation of pro-survival targets, and apoptotic sensitization of colon cancer cells to 5-FU. Here, DROSHA is linked to malignant colon neoplasm.