{"entity": "researcher", "timestamp": "2026-08-20T21:02:27.694Z", "family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "affiliations": ["Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, S-171 64, Stockholm, Sweden. ulrika.warpmanberglund@scilifelab.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db"}}, "publications": [{"entity": "publication", "iuid": "65cc0d5ba10243bca3912b74fb5ae7db", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/65cc0d5ba10243bca3912b74fb5ae7db.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/65cc0d5ba10243bca3912b74fb5ae7db"}}, "title": "Data from Inhibition of Oxidized Nucleotide Sanitation By TH1579 and Conventional Chemotherapy Cooperatively Enhance Oxidative DNA Damage and Survival in AML", "authors": [{"family": "Centio", "given": "Anders", "initials": "A", "orcid": "0000-0002-9449-8123", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06fa3c40ce4e42d08a2decc2c31fb999.json"}}, {"family": "Estruch", "given": "Montserrat", "initials": "M", "orcid": "0000-0002-7162-4158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e189e53cbfa47948171e1ae2e333f20.json"}}, {"family": "Reckzeh", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6391-625X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8be435d384a94651b2c4bb755a42635e.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Vittori", "given": "Camilla", "initials": "C", "orcid": "0000-0001-9441-8982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fc343c36814461891e49adc308c0d7a.json"}}, {"family": "Engelhard", "given": "Sophia", "initials": "S", "orcid": "0000-0003-1583-1010", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0a2461ac33742e5a14fec68c4219522.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Theilgaard-M\u00f6nch", "given": "Kim", "initials": "K", "orcid": "0000-0002-4239-4939", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/622932c3f158460b845d61ce15ca7345.json"}}], "type": "posted-content", "published": "2023-04-03", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1158/1535-7163.c.6543309.v1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:12:34.754Z", "modified": "2026-08-20T12:12:35.023Z"}, {"entity": "publication", "iuid": "f1d5c63874ab42a299e12ca5c08eeb83", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f1d5c63874ab42a299e12ca5c08eeb83.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f1d5c63874ab42a299e12ca5c08eeb83"}}, "title": "Overexpressed c-Myc Sensitizes Cells to TH1579, a Mitotic Arrest and Oxidative DNA Damage Inducer.", "authors": [{"family": "Henriksson", "given": "Sofia", "initials": "S"}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jos\u00e9 Manuel", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06bf2684da93449381c951c32dc14703.json"}}, {"family": "Solvie", "given": "Daniel", "initials": "D", "orcid": "0000-0003-4529-667X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5557da3d375f4a81ac9c29d36875b7d4.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2022-11-29", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "12", "issue": "12", "issn-l": null}, "abstract": "Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation.", "doi": "10.3390/biom12121777", "pmid": "36551206", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9775511"}, {"db": "pii", "key": "biom12121777"}], "notes": [], "created": "2026-08-20T13:38:42.021Z", "modified": "2026-08-20T13:38:42.136Z"}, {"entity": "publication", "iuid": "b1e3052a77514a259909d4d737df4580", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b1e3052a77514a259909d4d737df4580.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b1e3052a77514a259909d4d737df4580"}}, "title": "Overexpressed C-Myc Sensitize Cells to TH1579, an Mitotic Arrest and Oxidative DNA Damage Inducer", "authors": [{"family": "Henriksson", "given": "Sofia", "initials": "S"}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jos\u00e9 Manuel", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06bf2684da93449381c951c32dc14703.json"}}, {"family": "Solvie", "given": "Daniel", "initials": "D"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "posted-content", "published": "2022-08-22", "journal": {"issn-l": null}, "abstract": null, "doi": "10.20944/preprints202208.0369.v1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:56:32.667Z", "modified": "2026-08-20T12:56:32.691Z"}, {"entity": "publication", "iuid": "5c5bfa7eea964cf7961bdec3453b5d92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92"}}, "title": "Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f4696e361fe4aa3823d263674d1a498.json"}}, {"family": "Ben\u00edtez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Calvo", "given": "Patricia A", "initials": "PA"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c62ba219d3e34662aaa458dbd361cf31.json"}}, {"family": "Davies", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-4986-8594", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e74e0781a72d480c8e705a9a824e5e5a.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3601a5a4d88f4452b6d1ac5f22c79d9f.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Albers", "given": "Julian J", "initials": "JJ", "orcid": "0000-0001-9579-6360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8278cc4e9e7e4bde823f672b1982591d.json"}}, {"family": "Casta\u00f1eda-Zegarra", "given": "Sergio", "initials": "S", "orcid": "0000-0002-2808-6788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3438015dbc1d41b797a02c25a37fef60.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": 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{"family": "Haslene-Hox", "given": "Hanne", "initials": "H"}, {"family": "Loevenich", "given": "Simon", "initials": "S", "orcid": "0000-0001-5424-8755", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a06b60008414ef09b0c1e360ae1d10f.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Mamonov", "given": "Kirill", "initials": "K", "orcid": "0000-0001-5971-4305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2aeb36f9611f4c03883b8def30565da1.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F", "orcid": "0000-0002-0458-5187", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2e13b716bc349eb9dac083d7f801549.json"}}, {"family": "Sch\u00f6mberg", "given": "Fritz", "initials": "F", "orcid": "0000-0003-0092-0627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f10b06057e94d03a44967cce431c1a8.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Stewart", "given": "Josephine", "initials": "J"}, {"family": "D'Arcy-Evans", "given": "Nicholas", "initials": "N"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Michel", "given": "Dana", "initials": "D"}, {"family": "de Ory", "given": "Ana", "initials": "A"}, {"family": "Acero", "given": "Lucia", "initials": "L", "orcid": "0000-0001-8101-5412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af80832b8d8c4019bea17c15fa7651e2.json"}}, {"family": "Calvete", "given": "Oriol", "initials": "O", "orcid": "0000-0002-2623-2876", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ee0251167344b24b97b971b8c750795.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdce0df415d54e9d84a4fcbb4d1350e5.json"}}, {"family": "Hertweck", "given": "Christian", "initials": "C", "orcid": "0000-0002-0367-337X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b1f3fa37a7d4378b06381c2e68a10cb.json"}}, {"family": "Vilotijevic", "given": "Ivan", "initials": "I", "orcid": "0000-0001-6199-0632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eec3fc0f230046ccbe7ff46b2da70792.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C", "orcid": "0000-0001-7004-7048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9c7121a5e14414b8bace2708e8add2f.json"}}, {"family": "Osorio", "given": "Ana", "initials": "A", "orcid": "0000-0001-8124-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ecd4cc9c17d43009703efb95d979e09.json"}}, {"family": "Perona", "given": "Rosario", "initials": "R", "orcid": "0000-0002-2973-5153", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b116837f5c346d49e70ad5eb28d7afb.json"}}, {"family": "Stolz", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-3340-439X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4bde36f21953479a8762c1c858b4c451.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6196fa790b4645c3acef45a87cdac3d0.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2022-06-24", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "376", "issue": "6600", "pages": "1471-1476", "issn-l": "0036-8075"}, "abstract": "Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed \u03b2,\u03b4-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.", "doi": "10.1126/science.abf8980", "pmid": "35737787", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:29.051Z", "modified": "2026-08-20T11:59:30.134Z"}, {"entity": "publication", "iuid": "6315feb800e343aeb5d3716434ad0e92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6315feb800e343aeb5d3716434ad0e92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6315feb800e343aeb5d3716434ad0e92"}}, "title": "MTH1 Inhibitor TH588 Disturbs Mitotic Progression and Induces Mitosis-Dependent Accumulation of Genomic 8-oxodG.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Amaral", "given": "Nuno", "initials": "N"}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Groth", "given": "Petra", "initials": "P"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "17", "pages": "3530-3541", "issn-l": "0008-5472"}, "abstract": "Reactive oxygen species (ROS) oxidize nucleotide triphosphate pools (e.g., 8-oxodGTP), which may kill cells if incorporated into DNA. Whether cancers avoid poisoning from oxidized nucleotides by preventing incorporation via the oxidized purine diphosphatase MTH1 remains under debate. Also, little is known about DNA polymerases incorporating oxidized nucleotides in cells or how oxidized nucleotides in DNA become toxic. Here we show that replacement of one of the main DNA replicases in human cells, DNA polymerase delta (Pol \u03b4), with an error-prone variant allows increased 8-oxodG accumulation into DNA following treatment with TH588, a dual MTH1 inhibitor and microtubule targeting agent. The resulting elevated genomic 8-oxodG correlated with increased cytotoxicity of TH588. Interestingly, no substantial perturbation of replication fork progression was observed, but rather mitotic progression was impaired and mitotic DNA synthesis triggered. Reducing mitotic arrest by reversin treatment prevented accumulation of genomic 8-oxodG and reduced cytotoxicity of TH588, in line with the notion that mitotic arrest is required for ROS buildup and oxidation of the nucleotide pool. Furthermore, delayed mitosis and increased mitotic cell death was observed following TH588 treatment in cells expressing the error-prone but not wild-type Pol \u03b4 variant, which is not observed following treatments with antimitotic agents. Collectively, these results link accumulation of genomic oxidized nucleotides with disturbed mitotic progression. SIGNIFICANCE: These findings uncover a novel link between accumulation of genomic 8-oxodG and perturbed mitotic progression in cancer cells, which can be exploited therapeutically using MTH1 inhibitors.See related commentary by Alnajjar and Sweasy, p. 3459.", "doi": "10.1158/0008-5472.CAN-19-0883", "pmid": "32312836", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-0883"}], "notes": [], "created": "2026-08-20T12:10:55.392Z", "modified": "2026-08-20T12:10:55.497Z"}, {"entity": "publication", "iuid": "fcb2b1ddf30c442cbf7e5215e86263a7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fcb2b1ddf30c442cbf7e5215e86263a7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fcb2b1ddf30c442cbf7e5215e86263a7"}}, "title": "AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma.", "authors": [{"family": "Das", "given": "Ishani", "initials": "I", "orcid": "0000-0002-2019-8072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c39c73355c644713825f2c45a3d8ddd4.json"}}, {"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Tuominen", "given": "Rainer", "initials": "R"}, {"family": "H\u00f6iom", "given": "Veronica", "initials": "V"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Rajagopal", "given": "Varshni", "initials": "V"}, {"family": "Hansson", "given": "Johan", "initials": "J"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Egyh\u00e1zi Brage", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-0524-2346", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b1b43df8e774c498fd4e1e16b00a5fc.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Cell Death Differ.", "issn": "1476-5403", "volume": "27", "issue": "7", "pages": "2081-2098", "issn-l": "1350-9047"}, "abstract": "Cutaneous malignant melanoma (CMM) is the deadliest form of skin cancer and clinically challenging due to its propensity to develop therapy resistance. Reactive oxygen species (ROS) can induce DNA damage and play a significant role in CMM. MTH1 protein protects from ROS damage and is often overexpressed in different cancer types including CMM. Herein, we report that MTH1 inhibitor TH1579 induced ROS levels, increased DNA damage responses, caused mitotic arrest and suppressed CMM proliferation leading to cell death both in vitro and in an in vivo xenograft CMM zebrafish disease model. TH1579 was more potent in abrogating cell proliferation and inducing cell death in a heterogeneous co-culture setting when compared with CMM standard treatments, vemurafenib or trametinib, showing its broad anticancer activity. Silencing MTH1 alone exhibited similar cytotoxic effects with concomitant induction of mitotic arrest and ROS induction culminating in cell death in most CMM cell lines tested, further emphasizing the importance of MTH1 in CMM cells. Furthermore, overexpression of receptor tyrosine kinase AXL, previously demonstrated to contribute to BRAF inhibitor resistance, sensitized BRAF mutant and BRAF/NRAS wildtype CMM cells to TH1579. AXL overexpression culminated in increased ROS levels in CMM cells. Moreover, silencing of a protein that has shown opposing effects on cell proliferation, CAV-1, decreased sensitivity to TH1579 in a BRAF inhibitor resistant cell line. AXL-MTH1 and CAV-1-MTH1 mRNA expressions were correlated as seen in CMM clinical samples. Finally, TH1579 in combination with BRAF inhibitor exhibited a more potent cell killing effect in BRAF mutant cells both in vitro and in vivo. In summary, we show that TH1579-mediated efficacy is independent of BRAF/NRAS mutational status but dependent on the expression of AXL and CAV-1.", "doi": "10.1038/s41418-019-0488-1", "pmid": "31919461", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7308409"}, {"db": "pii", "key": "10.1038/s41418-019-0488-1"}], "notes": [], "created": "2026-08-20T08:49:15.889Z", "modified": "2026-08-20T08:49:16.042Z"}, {"entity": "publication", "iuid": "4639d73bc2ed4a338069b5f5a11165b0", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4639d73bc2ed4a338069b5f5a11165b0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4639d73bc2ed4a338069b5f5a11165b0"}}, "title": "Karonudib is a promising anticancer therapy in hepatocellular carcinoma.", "authors": [{"family": "Hua", "given": "Xiangwei", "initials": "X"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Gokturk", "given": "Camilla", "initials": "C"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Zhao", "given": "Zhenjun", "initials": "Z"}, {"family": "He", "given": "Kang", "initials": "K"}, {"family": "Feng", "given": "Mingxuan", "initials": "M"}, {"family": "Zang", "given": "Yunjin", "initials": "Y"}, {"family": "Zhang", "given": "Jianjun", "initials": "J"}, {"family": "Xia", "given": "Qiang", "initials": "Q"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}], "type": "journal article", "published": "2019-08-23", "journal": {"title": "Ther Adv Med Oncol", "issn": "1758-8340", "volume": "11", "pages": "1758835919866960", "issn-l": null}, "abstract": "Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent.\n\nMTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models.\n\nMTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib.\n\nAltogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future.", "doi": "10.1177/1758835919866960", "pmid": "31489034", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6710815"}, {"db": "pii", "key": "10.1177_1758835919866960"}], "notes": [], "created": "2026-08-20T12:17:13.598Z", "modified": "2026-08-20T12:17:13.697Z"}]}