Targeting death receptors in cancer with Apo2L/TRAIL.
Unlike conventional cancer therapeutics, death receptor ligands trigger tumor cell apoptosis independently of the p53 tumor suppressor gene, which frequently is inactivated in cancer. The death receptor ligand Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) offers promising therapeutic potential based on its ability to induce apoptosis in various cancer cell lines with little toxicity toward normal cells. Moreover, Apo2L/TRAIL displays single-agent activity and cooperates with chemotherapy or radiotherapy in a variety of tumor xenograft mouse models. Thus, Apo2L/TRAIL might be effective against tumors that have acquired resistance to conventional therapy, and could augment the efficacy of current treatment in a wide spectrum of cancers.
Kelley
Sean K
SK
Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. skelley@gene.com
Ashkenazi
Avi
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology* / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology* / Q000627:therapeutic use*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; C505640:Tnfrsf10b protein, mouse; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha