title: Manipulating the apoptotic pathway: potential therapeutics for cancer patients.
abstract: This review summarizes the current state of scientific understanding of the apoptosis pathway, with a focus on the proteins involved in the pathway, their interactions and functions. This forms the rationale for detailing the preclinical and clinical pharmacology of drugs that modulate the pivotal proteins in this pathway, with emphasis on drugs that are furthest advanced in clinical development as anticancer agents. There is a focus on describing drugs that modulate three of the most promising targets in the apoptosis pathway, namely antibodies that bind and activate the death receptors, small molecules that inhibit the anti-apoptotic Bcl-2 family proteins, and small molecules and antisense oligonucleotides that inactivate the inhibitors of apoptosis, all of which drive the equilibrium of the apoptotic pathway towards apoptosis. These structurally different yet functionally related groups of drugs represent a promising novel approach to anticancer therapeutics whether used as monotherapy or in combination with either classical cytotoxic or other molecularly targeted anticancer agents.
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, The Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Darcy J P
authors.initials: DJ
authors.lastname: Bates
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053218:Receptors, Death Domain / Q000819:agonists; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D053218:Receptors, Death Domain
keywords: Bcl-2 protein family; apoptosis; death domain receptors; inhibitors of apoptosis proteins