title: Molecular targeted therapies for diffuse large B-cell lymphoma based on apoptosis profiles.
abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult non-Hodgkin lymphoma and is treated with chemotherapy in combination with rituximab. Despite this aggressive therapy, the disease is fatal in 30-40% of patients. Inhibition of the apoptosis signalling pathways is strongly related to response to chemotherapy and eventual clinical outcome. In order to survive, lymphoma cells depend on disruption of the apoptosis pathway by mutations in apoptosis inducing genes or by continuous expression of anti-apoptotic proteins. The development of molecules targeting these apoptosis inhibitors provides a very promising opportunity to specifically target tumour cells without toxicity to non-malignant cells in DLBCL patients. Sensitivity for most of these antagonists can be predicted based on biological markers, suggesting the possibility of pre-defining patients who will most likely benefit from these targeted therapies. Experimental therapies aimed at restoring the upstream apoptosis pathway or targeting apoptosis inhibitors are currently being tested in clinical trials and are expected to be effective particularly in chemotherapy-refractory DLBCL, providing hope for patients who are refractory to current therapies.
authors.affiliation: Department of Clinical Pathology, VU University Medical Center, Amsterdam, The Netherlands. sagm.cillessen@vumc.nl
authors.forename: Saskia A G M
authors.initials: SA
authors.lastname: Cillessen
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Michitaka
authors.initials: M
authors.lastname: Notoya
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins