title: Drugs interfering with apoptosis in breast cancer.
abstract: Apoptosis plays an important role in development, growth, differentiation, altered gravity conditions, tissue homeostasis, immune defense, and cancer. It can be initiated by external signals via death receptors, but may also emerge from mitochondria. Today most of the key players in cellular apoptosis regulation are identified and can be targeted by therapeutic strategies. In this review we focus on recent development of drugs, which interfere with apoptosis and are currently used or tested for treatment of breast cancer. These novel agents include those targeting the extrinsic pathway such as Fas, tumor necrosis factor-alpha and tumor necrosis factor related apoptosis-inducing ligand, as well as drugs targeting the intrinsic Bcl-2 family pathway, or drugs inhibiting repair enzymes such as Poly (ADP-ribose) polymerase (PARP) inhibitors. Their function will be explained, their role in tumor biology and actual clinical studies will be discussed.
authors.affiliation: Department of Pharmacology, Aarhus University, Denmark. daniela.grimm@farm.au.dk
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Jessica
authors.initials: J
authors.lastname: Pietsch
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D020169:Caspases / Q000378:metabolism; D055808:Drug Discovery; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases