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Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling.
Teleanu, Maria-Veronica; Fuss, Carmina T; Paramasivam, Nagarajan; Pirmann, Sebastian; Mock, Andreas; Terkamp, Christoph; Kircher, Stefan; Landwehr, Laura-Sophie; Lenschow, Christina; Schlegel, Nicolas; Stenzinger, Albrecht; Jahn, Arne; Fassnacht, Martin; Glimm, Hanno; Hübschmann, Daniel; Fröhling, Stefan; Kroiss, Matthias.
Afiliación
  • Teleanu MV; Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fuss CT; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Germany.
  • Paramasivam N; Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Germany.
  • Pirmann S; Computational Oncology Group, Molecular Precision Oncology Program, NCT Heidelberg and DKFZ, Germany.
  • Mock A; Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Terkamp C; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
  • Kircher S; Institute of Pathology, University of Würzburg, Germany.
  • Landwehr LS; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Germany.
  • Lenschow C; Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Germany.
  • Schlegel N; Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Germany.
  • Stenzinger A; Institute of Pathology, Heidelberg University Hospital, Germany.
  • Jahn A; Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Germany.
  • Fassnacht M; ERN-GENTURIS, Hereditary Cancer Syndrome Center Dresden, Germany.
  • Glimm H; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Germany.
  • Hübschmann D; Comprehensive Cancer Center Mainfranken, University of Würzburg, Germany.
  • Fröhling S; Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
  • Kroiss M; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mol Oncol ; 17(7): 1343-1355, 2023 07.
Article en En | MEDLINE | ID: mdl-36808802
Parathyroid carcinoma (PC) is an ultra-rare malignancy with a high risk of recurrence after surgery. Tumour-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (a) immune checkpoint inhibition with pembrolizumab based on high tumour mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (b) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 (Fibroblast Growth Factor Receptor 1) and RET (Ret Proto-Oncogene) and, (c) later in the course of the disease, PARP (Poly(ADP-Ribose) Polymerase) inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome-wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra-rare cancers based on insight into disease biology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de las Paratiroides / Carcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de las Paratiroides / Carcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos