title: HER2 as a novel therapeutic target for cervical cancer.
abstract: Surgery and radiation are the current standard treatments for cervical cancer. However, there is no effective therapy for metastatic or recurrent cases, necessitating the identification of therapeutic targets. In order to create preclinical models for screening potential therapeutic targets, we established 14 patient-derived xenograft (PDX) models of cervical cancers using subrenal implantation methods. Serially passaged PDX tumors retained the histopathologic and genomic features of the original tumors. Among the 9 molecularly profiled cervical cancer patient samples, a HER2-amplified tumor was detected by array comparative genomic hybridization and targeted next-generation sequencing. We confirmed HER2 overexpression in the tumor and serially passaged PDX. Co-administration of trastuzumab and lapatinib in the HER2-overexpressed PDX significantly inhibited tumor growth compared to the control. Thus, we established histopathologically and genomically homologous PDX models of cervical cancer using subrenal implantation. Furthermore, we propose HER2 inhibitor-based therapy for HER2-amplified cervical cancer refractory to conventional therapy.
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Doo-Yi
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seokhwi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Ensel
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Jung
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
authors.forename: Suzie E
authors.initials: SE
authors.lastname: Ahn
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.|Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.|Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000077341:Lapatinib; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2; cervical cancer; patient-derived xenograft; targeted therapy; trastuzumab