{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:50:07Z","timestamp":1781272207840,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["INST 337\/15-1"],"award-info":[{"award-number":["INST 337\/15-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["INST 337\/16-1"],"award-info":[{"award-number":["INST 337\/16-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["INST 152\/837-1"],"award-info":[{"award-number":["INST 152\/837-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["INST 152\/947-1 FUGG"],"award-info":[{"award-number":["INST 152\/947-1 FUGG"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["SCHL 406\/21-1"],"award-info":[{"award-number":["SCHL 406\/21-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Remarkable differences exist in the outcome of systemic cancer therapies. Lymphomas and leukemias generally respond well to systemic chemotherapies, while solid cancers often fail. We engineered different human cancer cells lines to uniformly express a modified herpes simplex virus thymidine kinase TK.007 as a suicide gene when ganciclovir (GCV) is applied, thus in theory achieving a similar response in all cell lines. Methods: Fifteen different cell lines were engineered to express the TK.007 gene. XTT-cell proliferation assays were performed and the IC50-values were calculated. Functional kinome profiling, mRNA sequencing, and bottom-up proteomics analysis with Ingenuity pathway analysis were performed. Results: GCV potency varied among cell lines, with lymphoma and leukemia cells showing higher susceptibility than solid cancer cells. Functional kinome profiling implies a contribution of the SRC family kinases and decreased overall kinase activity. mRNA sequencing highlighted alterations in the MAPK pathways and bottom-up proteomics showed differences in apoptotic and epithelial junction signaling proteins. Conclusions: The histogenetic origin of cells influenced the susceptibility of human malignant cells towards cytotoxic agents with leukemias and lymphomas being more sensitive than solid cancer cells.<\/jats:p>","DOI":"10.3390\/cancers16122278","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T11:47:17Z","timestamp":1718797637000},"page":"2278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Histogenetic Origin of Malignant Cells Predicts Their Susceptibility towards Synthetic Lethality Utilizing the TK.007 System"],"prefix":"10.3390","volume":"16","author":[{"given":"Fabian Bernhard","family":"Pallasch","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Medical Center\u2014University of Freiburg, 79106 Freiburg Im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Freytag","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kriegs","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Radiation Oncology, Hubertus Wald Tumorzentrum\u2013University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"UCCH Kinomics Core Facility, Hubertus Wald Tumorzentrum\u2013University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Gatzemeier","sequence":"additional","affiliation":[{"name":"Section Mass Spectrometric and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-7498","authenticated-orcid":false,"given":"Thomas","family":"Mair","sequence":"additional","affiliation":[{"name":"Section Mass Spectrometric and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Voss","sequence":"additional","affiliation":[{"name":"Section Mass Spectrometric and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-6766","authenticated-orcid":false,"given":"Kristoffer","family":"Riecken","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-7211","authenticated-orcid":false,"given":"Boris","family":"Fehse","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-7036","authenticated-orcid":false,"given":"Hartmut","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Section Mass Spectrometric and Proteomics, Center of Diagnostics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Department of Medicine, Medical School Berlin, Mecklenburgische Strasse 57, 14197 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of deaths from cancer caused by metastases?","volume":"8","author":"Rogers","year":"2019","journal-title":"Cancer Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcancer.2016.09.002","article-title":"Novel biomarkers in cancer: The whole is greater than the sum of its parts","volume":"45","author":"Samatov","year":"2017","journal-title":"Semin. 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