text: In vivo anti-tumor activity of thalidomide is believed to be due to the potent anti-angiogenic effect and also through changes in cytokine expression. In vitro assays on apoptosis in MM cells have been shown, when treated with thalidomide and its analogs, to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 leading to indirect upregulation of caspase-9 activity. Further anti-tumor activity is mediated through the inhibition of apoptosis protein-2 and pro-survival effects of IGF-1, increasing sensitivity to FAS mediated cell death and enhancement of TNF-related apoptosis inducing ligand. They have also been shown to cause dose dependent G0/G1 cell cycle arrest in leukemia cell lines where the analogs showed 100 times more potency than thalidomide.