title: STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma.
abstract: Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL), a class of nongerminal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof of concept that STAT3 is an effective molecular target for ABC-like DLBCL therapy. Direct inhibition of STAT3 with short hairpin RNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression of STAT3 target genes, and inhibition of a tumor-promoting microenvironment. Together, these results suggest that STAT3 is essential to maintain the pathophysiology of ABC-like DLBCL and therefore that STAT3 inhibition may offer a promising approach in its therapy.
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. ascuto@coh.org
authors.forename: Anna
authors.initials: A
authors.lastname: Scuto
authors.forename: Maciej
authors.initials: M
authors.lastname: Kujawski
authors.forename: Claudia
authors.initials: C
authors.lastname: Kowolik
authors.forename: Ludmila
authors.initials: L
authors.lastname: Krymskaya
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: David
authors.initials: D
authors.lastname: Digiusto
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human