title: Tumor-Targeting Salmonella typhimurium A1-R Sensitizes Melanoma With a BRAF-V600E Mutation to Vemurafenib in a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model.
abstract: Previously, a BRAF-V600E-mutant melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. Trametinib (TRA), an MEK inhibitor, caused tumor regression. In contrast, another MEK inhibitor, cobimetinib (COB) could slow but not arrest growth or cause regression of the melanoma PDOX. First-line therapy temozolomide (TEM) could slow but not arrest tumor growth or cause regression. In addition, vemurafenib (VEM) was not effective even though VEM is supposed to target the BRAF-V600E mutation. We also previously demonstrated that tumor-targeting with S. typhimurium A1-R combined with TEM was significantly more effective than either S. typhimurium A1-R alone or TEM alone on the melanoma PDOX with the BRAF-V600E mutation. The present study used this PDOX model of melanoma to test its sensitivity to VEM combined with S. typhimurium A1-R compared to VEM alone and VEM combined with COB. VEM combined with S. typhimurium A1-R was significantly more effective than VEM alone or VEM combined with COB (P = 0.0216) which is currently first line therapy for advanced melanoma with a BRAF-V600E mutation. J. Cell. Biochem. 118: 2314-2319, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.|Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: AntiCancer, Inc., San Diego, California.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: AntiCancer, Inc., San Diego, California.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Hematology-Oncology, University of California, Los Angeles, California.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kiyuna
authors.affiliation: Department of Pathology, University of California, Los Angeles, California.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Nelson
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Russell
authors.affiliation: Department of Pathology, University of California, Los Angeles, California.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Dry
authors.affiliation: Department of Pathology, University of California, Los Angeles, California.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California.|PDOX Inc., San Diego, California.
authors.forename: Fritz C
authors.initials: FC
authors.lastname: Eilber
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.|PDOX Inc., San Diego, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000368:Aged; D000818:Animals; D001384:Azetidines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D010880:Piperidines / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D012486:Salmonella typhimurium / Q000235:genetics / Q000502:physiology*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib; D023041:Xenograft Model Antitumor Assays
chemical_list: D001384:Azetidines; D007211:Indoles; D010880:Piperidines; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; D048493:Proto-Oncogene Proteins B-raf; C574276:cobimetinib
keywords: COBIMETINIB; COMBINATION THERAPY; DRUG-RESPONSE; MELANOMA; NUDE MICE; ORTHOTOPIC; PDOX; PRECISION MEDICINE; Salmonella typhimurium A1-R; TUMOR REGRESSION; VEMURAFENIB