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Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that displays nearly ubiquitous cancer-specific toxicity, with no harmful effects toward normal cells or tissues.mda7/IL-24 was cloned from human melanoma cells in our laboratory by differentiation induction subtraction hybridization (DISH).This gene promotes endoplasmic reticulum (ER) stress culminating in apoptosis or toxic autophagy in a broadspectrum of human cancers, when assayed in cell culture, in vivo in human tumor xenograft mouse models and in a Phase Ⅰ clinical trial in patients with advanced cancers.