{"entity": "researcher", "timestamp": "2026-07-20T00:15:45.472Z", "family": "Friedrich", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3889-5589", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, Science for Laboratory, Solna, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb"}}, "publications": [{"entity": "publication", "iuid": "362c451c88124be69c423cc4853c5216", "links": {"self": {"href": "https://publications.scilifelab.se/publication/362c451c88124be69c423cc4853c5216.json"}, "display": {"href": "https://publications.scilifelab.se/publication/362c451c88124be69c423cc4853c5216"}}, "title": "Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones.", "authors": [{"family": "Marklund", "given": "Maja", "initials": "M", "orcid": "0000-0003-2627-2437", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a238f7adbc242398a46fd24190a2811.json"}}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Friedrich", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3889-5589", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb.json"}}, {"family": "Berglund", "given": "Emelie", "initials": "E", "orcid": "0000-0003-1857-307X", "researcher": {"href": "https://publications.scilifelab.se/researcher/87df6f4e3aed48938e7bee3acf27847e.json"}}, {"family": "Tarish", "given": "Firas", "initials": "F"}, {"family": "Tanoglidi", "given": "Anna", "initials": "A"}, {"family": "Liu", "given": "Yao", "initials": "Y", "orcid": "0000-0001-5572-723X", "researcher": {"href": "https://publications.scilifelab.se/researcher/08bfef572b6e4c7287380d8a5783bd9c.json"}}, {"family": "Bergenstr\u00e5hle", "given": "Ludvig", "initials": "L", "orcid": "0000-0002-5108-4481", "researcher": {"href": "https://publications.scilifelab.se/researcher/98234e5e06c241879f6f986ded3ab6f9.json"}}, {"family": "Erickson", "given": "Andrew", "initials": "A"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Lamb", "given": "Alastair D", "initials": "AD", "orcid": "0000-0002-2968-7155", "researcher": {"href": "https://publications.scilifelab.se/researcher/798d88b3df1e4a7d994e90b5d60372e6.json"}}, {"family": "Sonnhammer", "given": "Erik", "initials": "E", "orcid": "0000-0002-9015-5588", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d7888c298484f958c2c5f7fe0a8a9ba.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}], "type": "journal article", "published": "2022-09-17", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "13", "issue": "1", "pages": "5475"}, "abstract": "The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors.", "doi": "10.1038/s41467-022-33069-3", "pmid": "36115838", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service", "NGI Spatial omics": null}, "xrefs": [{"db": "pmc", "key": "PMC9482614"}, {"db": "pii", "key": "10.1038/s41467-022-33069-3"}], "notes": [], "created": "2022-12-19T10:35:54.516Z", "modified": "2023-10-23T09:22:51.156Z"}, {"entity": "publication", "iuid": "9acd4142dc314a259044f6bf390a903b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9acd4142dc314a259044f6bf390a903b"}}, "title": "MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.", "authors": [{"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jos\u00e9 Manuel", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications.scilifelab.se/researcher/474af64ef5914eb7b99f9d98bf9a7455.json"}}, {"family": "Pham", "given": "Therese M", "initials": "TM"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "Tsuber", "given": "Viktoriia", "initials": "V"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A"}, {"family": "Heshmati", "given": "Yaser", "initials": "Y"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Nagesh Danda", "given": "Akhilesh", "initials": "A"}, {"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Friedrich", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3889-5589", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e1de4177ae649aba93a633ca451ebdb.json"}}, {"family": "Centio", "given": "Anders", "initials": "A"}, {"family": "Estruch", "given": "Montserrat", "initials": "M", "orcid": "0000-0002-7162-4158", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf0c60406fc74282b87f74170571d297.json"}}, {"family": "V\u00e5tsveen", "given": "Thea Kristin", "initials": "TK"}, {"family": "Struyf", "given": "Nona", "initials": "N", "orcid": "0000-0002-6975-0753", "researcher": {"href": "https://publications.scilifelab.se/researcher/1295c3be31024c4fa2da10cffe42c406.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Sandvall", "given": "Teresa", "initials": "T"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Theilgaard-M\u00f6nch", "given": "Kim", "initials": "K", "orcid": "0000-0002-4239-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac2392d2c784203b15e8ec53d6a746e.json"}}, {"family": "Garnett", "given": "Mathew J", "initials": "MJ", "orcid": "0000-0002-2618-4237", "researcher": {"href": "https://publications.scilifelab.se/researcher/81268f585935408e9a9673db9da394f6.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Walfridsson", "given": "Julian", "initials": "J"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}], "type": "journal article", "published": "2021-11-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "22", "pages": "5733-5744", "issn-l": "0008-5472"}, "abstract": "Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin-CD34+CD38-), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. SIGNIFICANCE: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.", "doi": "10.1158/0008-5472.CAN-21-0061", "pmid": "34593524", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9397639"}, {"db": "pii", "key": "0008-5472.CAN-21-0061"}], "notes": [], "created": "2023-11-27T21:58:04.269Z", "modified": "2024-01-16T13:48:38.121Z"}]}