title: The implication of FLT3 amplification for FLT targeted therapeutics in solid tumors.
abstract: We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3. Additional drug combinations with mTOR inhibitor did not affect the cell proliferation of PDC. FLT3 amplification in solid cancers is infrequently observed using targeted genomic profile, as yet, FLT3 amplification does not seem to be an actionable target or a proper biomarker for FLT3 inhibitor sensitivity.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soomin
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Nayoung K D
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Woongyang
authors.initials: W
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D000073359:Exome Sequencing; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051941:fms-Like Tyrosine Kinase 3
keywords: FLT3 amplification; regorafenib; solid tumors