Directing cancer cells to self-destruct with pro-apoptotic receptor agonists.
Each day, the human body eliminates billions of unwanted cells by apoptotic suicide. Apoptosis provides an important barrier against cancer; however, specific mutations enable some tumour cells to escape apoptotic death and become more malignant. Two signalling pathways initiate apoptosis: one acts through intracellular Bcl-2 proteins, the other through cell-surface pro-apoptotic receptors. New molecular insights have inspired the development of pro-apoptotic receptor agonists (PARAs), including the recombinant human protein apoptosis ligand 2/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) and agonistic monoclonal antibodies to its signalling receptors. Acting alone, or in concert with other agents, PARAs may overcome key apoptosis blocks and direct cancer cells to self-destruct.
Ashkenazi
Avi
A
Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080-4918, USA. aa@gene.com.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D015195:Drug Design; D053200:Fas-Associated Death Domain Protein / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D053218:Receptors, Death Domain / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004273:DNA, Neoplasm; D053200:Fas-Associated Death Domain Protein; D053218:Receptors, Death Domain