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We used whole\u2010genome 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\u2010base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide\u2010like) overactivation; (b) multi\u2010receptor tyrosine kinase inhibition with lenvatinib due to overexpression of\n                    <jats:italic>FGFR1<\/jats:italic>\n                    (Fibroblast Growth Factor Receptor 1) and\n                    <jats:italic>RET<\/jats:italic>\n                    (Ret Proto\u2010Oncogene) and, (c)\u00a0later in the course of the disease, PARP (Poly(ADP\u2010Ribose) 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\u2010wide 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\u2010rare cancers based on insight into disease biology.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13398","type":"journal-article","created":{"date-parts":[[2023,2,19]],"date-time":"2023-02-19T04:47:51Z","timestamp":1676782071000},"page":"1343-1355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-6158","authenticated-orcid":false,"given":"Maria\u2010Veronica","family":"Teleanu","sequence":"first","affiliation":[{"name":"Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg German Cancer Research Center (DKFZ)  Heidelberg 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