{"entity": "researcher", "timestamp": "2026-08-20T20:46:26.275Z", "family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73"}}, "publications": [{"entity": "publication", "iuid": "92b40b92d22e40b2a520241e3e3dd2a3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/92b40b92d22e40b2a520241e3e3dd2a3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/92b40b92d22e40b2a520241e3e3dd2a3"}}, "title": "Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.", "authors": [{"family": "Wang", "given": "Jiantao", "initials": "J"}, {"family": "Pouryaghoub", "given": "Nasim", "initials": "N"}, {"family": "Strauss", "given": "Robert", "initials": "R", "orcid": "0000-0003-1777-7177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ac310212e644deba1b8bf8a2a41a705.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2025-10-00", "journal": {"title": "Fundam Clin Pharmacol", "issn": "1472-8206", "volume": "39", "issue": "5", "pages": "e70044", "issn-l": null}, "abstract": "Cisplatin and its derivatives remain a cornerstone in the treatment of solid malignancies. Resistance is a major factor limiting their clinical utility.\n\nIn the present study, we set out to interrogate therapeutic approaches to target cisplatin-resistant cancer cells. We focused on therapies exploiting metabolic pathways that are altered in drug-resistant cells. We sought to find an existing therapy that has monotherapy efficacy against cisplatin-resistant cancer cells that can also re-sensitize to cisplatin.\n\nWe used lung and ovarian cancer cell lines with acquired resistance to cisplatin together with drug sensitivity assays, conducted both with monotherapies and cisplatin combinations.\n\nWe show that cancer cell lines with acquired resistance to cisplatin have altered levels of enzymes involved in glutamine metabolism, which can result in differential sensitivity to targeted agents. We show that expression of one of these enzymes-the glutamate-cystine antiporter SLC7A11, up-regulated 6-fold in a cisplatin-resistant lung cancer cell line-has potential prognostic significance in lung cancer but not ovarian cancer. After identifying a common dependency of cisplatin-resistant cancer cells upon extracellular glutamine, we then evaluate the utility of the long-standing anti-leukemic therapy asparaginase (ASNase)-which possesses both asparaginase and glutaminase activity-as a potential approach. We show ASNase preferentially inhibits the proliferation of cisplatin-resistant cancer cells and can potentially re-sensitize these cells to cisplatin.\n\nOur results underpin the prevalence of altered metabolism in cisplatin-resistant cells and highlight the potential utility of re-purposing ASNase to target these cells, warranting further investigation.", "doi": "10.1111/fcp.70044", "pmid": "40784667", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12335911"}], "notes": [], "created": "2026-08-20T11:17:50.563Z", "modified": "2026-08-20T11:17:50.663Z"}, {"entity": "publication", "iuid": "4b02678dd884479ab9e749a3c2fb1622", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4b02678dd884479ab9e749a3c2fb1622.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4b02678dd884479ab9e749a3c2fb1622"}}, "title": "Uridine cytidine kinases dictate the therapeutic response of molnupiravir via its bioactivation", "authors": [{"family": "Shu", "given": "Huazhang", "initials": "H"}, {"family": "Sharm", "given": "Sushma", "initials": "S"}, {"family": "Alam", "given": "Seher", "initials": "S"}, {"family": "Frank", "given": "Lilian", "initials": "L"}, {"family": "Tampere", "given": "Marianna", "initials": "M"}, {"family": "van Kuilenburg", "given": "Andr\u00e9 B P", "initials": "ABP"}, {"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48bb9c8ab8a5465a8a4da1997f1af56d.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M"}, {"family": "Chabes", "given": "Andrei", "initials": "A"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}], "type": "posted-content", "published": "2025-05-14", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.05.13.653844", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:03:49.928Z", "modified": "2026-08-20T11:05:18.913Z"}, {"entity": "publication", "iuid": "e8a7f3c98b344f20863ac4cd24bd5507", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e8a7f3c98b344f20863ac4cd24bd5507.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e8a7f3c98b344f20863ac4cd24bd5507"}}, "title": "Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action.", "authors": [{"family": "Hormann", "given": "Femke M", "initials": "FM", "orcid": "0000-0001-5164-3047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8868b55d9ca345f5b92aff76547e0e7c.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "3", "pages": "531-542", "issn-l": "0887-6924"}, "abstract": "T-cell acute lymphoblastic leukemia (T-ALL) patients often have a poor 5-year event-free survival. The only T-ALL specific drug in clinical practice is nelarabine. A prodrug of the deoxyguanosine analog ara-G, nelarabine is a rationally designed agent selective for the treatment of T-cell malignancies. Originally approved for relapsed/refractory T-ALL, it is increasingly used in T-ALL therapy and is currently being evaluated in upfront treatment. Whilst the clinical use of nelarabine has been the topic of multiple review articles, a thorough overview of the preclinical data detailing the molecular underpinnings of its anti-leukemic activity is lacking, which is critical to inform mechanism-based use. Thus, in the present article we conducted a semi-systematic review of the literature and critically evaluated the preclinical knowledge on the molecular pharmacology of nelarabine. Whilst early studies identified ara-G triphosphate to be the principal active metabolite and nuclear DNA synthesis to be a key target, many fundamental questions remain that could inform upon future use of this therapy. These include the nature of nelarabine-induced DNA lesions and their repair, together with additional cellular targets of ara-G metabolites and their role in efficacy and toxicity. A critical avenue of research in need of development is investigation of nelarabine combination therapies, both in the context of current T-ALL chemotherapy regimens and with emerging anti-leukemic agents, and we highlight some areas to pursue. Altogether, we discuss what we can learn from the preclinical literature as a whole and present our view for future research regarding nelarabine treatment in T-ALL.", "doi": "10.1038/s41375-025-02529-2", "pmid": "39962329", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11879874"}, {"db": "pii", "key": "10.1038/s41375-025-02529-2"}], "notes": [], "created": "2026-08-20T08:47:23.157Z", "modified": "2026-08-20T08:47:49.089Z"}, {"entity": "publication", "iuid": "6315428314a64702a9021607e1e7f809", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6315428314a64702a9021607e1e7f809.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6315428314a64702a9021607e1e7f809"}}, "title": "Understanding the interplay between dNTP metabolism and genome stability in cancer.", "authors": [{"family": "Yag\u00fce-Capilla", "given": "Miriam", "initials": "M", "orcid": "0000-0002-9643-9960", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9281ad99026b48d682e4f794016ff104.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2024-08-01", "journal": {"title": "Dis Model Mech", "issn": "1754-8411", "volume": "17", "issue": "8", "issn-l": null}, "abstract": "The size and composition of the intracellular DNA precursor pool is integral to the maintenance of genome stability, and this relationship is fundamental to our understanding of cancer. Key aspects of carcinogenesis, including elevated mutation rates and induction of certain types of DNA damage in cancer cells, can be linked to disturbances in deoxynucleoside triphosphate (dNTP) pools. Furthermore, our approaches to treat cancer heavily exploit the metabolic interplay between the DNA and the dNTP pool, with a long-standing example being the use of antimetabolite-based cancer therapies, and this strategy continues to show promise with the development of new targeted therapies. In this Review, we compile the current knowledge on both the causes and consequences of dNTP pool perturbations in cancer cells, together with their impact on genome stability. We outline several outstanding questions remaining in the field, such as the role of dNTP catabolism in genome stability and the consequences of dNTP pool expansion. Importantly, we detail how our mechanistic understanding of these processes can be utilised with the aim of providing better informed treatment options to patients with cancer.", "doi": "10.1242/dmm.050775", "pmid": "39206868", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11381932"}, {"db": "pii", "key": "361806"}], "notes": [], "created": "2026-08-20T12:38:29.408Z", "modified": "2026-08-20T12:38:29.515Z"}, {"entity": "publication", "iuid": "35507cf3450745f497420acc2010ae06", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/35507cf3450745f497420acc2010ae06.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/35507cf3450745f497420acc2010ae06"}}, "title": "Glutamine-addiction in cisplatin resistant cancer cells is mediated by SLC7A11 and can be targeted with asparaginase therapy", "authors": [{"family": "Wang", "given": "Jiantao", "initials": "J", "orcid": "0000-0001-6397-9429", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/736395487707411b80d10ef2dd597168.json"}}, {"family": "Strauss", "given": "Robert", "initials": "R", "orcid": "0000-0003-1777-7177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ac310212e644deba1b8bf8a2a41a705.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "posted-content", "published": "2024-07-22", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.07.19.604261", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:55:44.095Z", "modified": "2026-08-20T10:55:44.226Z"}, {"entity": "publication", "iuid": "39ef00ee5aae40fdae3a7b8dd287912a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/39ef00ee5aae40fdae3a7b8dd287912a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/39ef00ee5aae40fdae3a7b8dd287912a"}}, "title": "Targeting pan-essential pathways in cancer with cytotoxic chemotherapy: challenges and opportunities.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2023-10-00", "journal": {"title": "Cancer Chemother. Pharmacol.", "issn": "1432-0843", "volume": "92", "issue": "4", "pages": "241-251", "issn-l": "0344-5704"}, "abstract": "Cytotoxic chemotherapy remains a key modality in cancer treatment. These therapies, successfully used for decades, continue to transform the lives of cancer patients daily. With the high attrition rate of current oncology drug development, combined with the knowledge that most new therapies do not displace standard-of-care treatments and that many healthcare systems cannot afford these new therapies; cytotoxic chemotherapies will remain an important component of cancer therapy for many years to come. The clinical value of these therapies is often under-appreciated within the pre-clinical cancer research community, where this diverse class of agents are often grouped together as non-specific cellular poisons killing tumor cells based solely upon proliferation rate; however, this is inaccurate. This review article seeks to reaffirm the importance of focusing research efforts upon improving our basic understanding of how these drugs work, discussing their ability to target pan-essential pathways in cancer cells, the relationship of this to the chemotherapeutic window, and highlighting basic science approaches that can be employed towards refining their use.", "doi": "10.1007/s00280-023-04562-3", "pmid": "37452860", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10435635"}, {"db": "pii", "key": "10.1007/s00280-023-04562-3"}], "notes": [], "created": "2026-08-20T06:39:42.328Z", "modified": "2026-08-20T06:39:42.364Z"}, {"entity": "publication", "iuid": "731ee047142a4f8cb2afa616fd06200d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/731ee047142a4f8cb2afa616fd06200d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/731ee047142a4f8cb2afa616fd06200d"}}, "title": "Targeting the DNA damage response and repair in cancer through nucleotide metabolism.", "authors": [{"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "16", "issue": "21", "pages": "3792-3810", "issn-l": "1574-7891"}, "abstract": "The exploitation of the DNA damage response and DNA repair proficiency of cancer cells is an important anticancer strategy. The replication and repair of DNA are dependent upon the supply of deoxynucleoside triphosphate (dNTP) building blocks, which are produced and maintained by nucleotide metabolic pathways. Enzymes within these pathways can be promising targets to selectively induce toxic DNA lesions in cancer cells. These same pathways also activate antimetabolites, an important group of chemotherapies that disrupt both nucleotide and DNA metabolism to induce DNA damage in cancer cells. Thus, dNTP metabolic enzymes can also be targeted to refine the use of these chemotherapeutics, many of which remain standard of care in common cancers. In this review article, we will discuss both these approaches exemplified by the enzymes MTH1, MTHFD2 and SAMHD1. \u00a9 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.", "doi": "10.1002/1878-0261.13227", "pmid": "35583750", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9627788"}], "notes": [], "created": "2026-08-20T06:26:48.146Z", "modified": "2026-08-20T06:26:48.211Z"}, {"entity": "publication", "iuid": "b6c66840b2114e39b96ee7d129873f67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b6c66840b2114e39b96ee7d129873f67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b6c66840b2114e39b96ee7d129873f67"}}, "title": "Correction: Mutant p53-reactivating compound APR-246 synergizes with asparaginase in inducing growth suppression in acute lymphoblastic leukemia cells.", "authors": [{"family": "Ceder", "given": "Sophia", "initials": "S", "orcid": "0000-0002-6195-9288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e3941e3b2ffa422ca626b3b37dc78b0a.json"}}, {"family": "Eriksson", "given": "Sofi E", "initials": "SE"}, {"family": "Liang", "given": "Ying Yu", "initials": "YY"}, {"family": "Cheteh", "given": "Emarndeena H", "initials": "EH"}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Fujihara", "given": "Kenji M", "initials": "KM", "orcid": "0000-0002-8387-4912", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f39a031e754da197e2a7589db59416.json"}}, {"family": "Bianchi", "given": "Julie", "initials": "J", "orcid": "0000-0001-7958-4261", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5a6a8d91db5743a5928b4a02e7fd1aed.json"}}, {"family": "Bykov", "given": "Vladimir J N", "initials": "VJN", "orcid": "0000-0002-7199-8942", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b02643c742d4ed0b316359764ca103c.json"}}, {"family": "Abrahmsen", "given": "Lars", "initials": "L"}, {"family": "Clemons", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0001-9283-9978", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/705d15d93d6c4a06bcfec8fad5941a9d.json"}}, {"family": "Nordlund", "given": "P\u00e4r", "initials": "P"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Wiman", "given": "Klas G", "initials": "KG", "orcid": "0000-0002-7113-524X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/536683a931c44e32aa475e97f696e4ba.json"}}], "type": "published erratum", "published": "2022-08-03", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "13", "issue": "8", "pages": "672", "issn-l": "2041-4889"}, "abstract": null, "doi": "10.1038/s41419-022-05130-y", "pmid": "35922423", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9349250"}, {"db": "pii", "key": "10.1038/s41419-022-05130-y"}], "notes": [], "created": "2026-08-20T08:49:47.856Z", "modified": "2026-08-20T08:49:47.915Z"}, {"entity": "publication", "iuid": "24ffe445302e4bdc9101206568c93fdb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/24ffe445302e4bdc9101206568c93fdb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/24ffe445302e4bdc9101206568c93fdb"}}, "title": "The prognostic and clinicopathological significance of desmoglein 2 in human cancers: a systematic review and meta-analysis.", "authors": [{"family": "Wang", "given": "Jiantao", "initials": "J"}, {"family": "Hao", "given": "Siyuan", "initials": "S"}, {"family": "Gu", "given": "Junjie", "initials": "J"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Wang", "given": "Yan", "initials": "Y"}], "type": "meta-analysis", "published": "2022-03-22", "journal": {"title": "PeerJ", "issn": "2167-8359", "volume": "10", "pages": "e13141", "issn-l": "2167-8359"}, "abstract": "The survival and clinicopathological significance of desmoglein 2 (DSG2) in various cancers is controversial. Thus, we performed this systematic review and meta-analysis to explore the preliminary prognostic value of DSG2.\n\nEligible studies were identified from databases including PubMed, the Cochrane Library, Embase, Web of Science and Scopus. Hand searches were also conducted in relevant bibliographies. We then extracted and pooled hazard ratio (HR) of overall survival (OS) and odds ratio (OR) of clinicopathological features.\n\nA total of 11 eligible studies containing 1,488 patients were included. Our results demonstrated that in non-small cell lung cancer (NSCLC), high DSG2 expression is associated with poor OS. However, in digestive system cancer and female reproductive system cancer, there were no statistically significant associations between OS and DSG2.\n\nBased on the findings of this study, high DSG2 expression is associated with worse prognosis in patients with NSCLC, and thus DSG2 expression could be a biomarker for prognosis in NSCLC.", "doi": "10.7717/peerj.13141", "pmid": "35345582", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8957267"}, {"db": "pii", "key": "13141"}], "notes": [], "created": "2026-08-20T13:56:52.715Z", "modified": "2026-08-20T13:56:52.737Z"}, {"entity": "publication", "iuid": "458ab4fc46c74b1bb0b3b492659a37a6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/458ab4fc46c74b1bb0b3b492659a37a6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/458ab4fc46c74b1bb0b3b492659a37a6"}}, "title": "Mutant p53-reactivating compound APR-246 synergizes with asparaginase in inducing growth suppression in acute lymphoblastic leukemia cells.", "authors": [{"family": "Ceder", "given": "Sophia", "initials": "S", "orcid": "0000-0002-6195-9288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e3941e3b2ffa422ca626b3b37dc78b0a.json"}}, {"family": "Eriksson", "given": "Sofi E", "initials": "SE"}, {"family": "Liang", "given": "Ying Yu", "initials": "YY"}, {"family": "Cheteh", "given": "Emarndeena H", "initials": "EH"}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Fujihara", "given": "Kenji M", "initials": "KM", "orcid": "0000-0002-8387-4912", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92f39a031e754da197e2a7589db59416.json"}}, {"family": "Bianchi", "given": "Julie", "initials": "J", "orcid": "0000-0001-7958-4261", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5a6a8d91db5743a5928b4a02e7fd1aed.json"}}, {"family": "Bykov", "given": "Vladimir J N", "initials": "VJN", "orcid": "0000-0002-7199-8942", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b02643c742d4ed0b316359764ca103c.json"}}, {"family": "Abrahmsen", "given": "Lars", "initials": "L"}, {"family": "Clemons", "given": "Nicholas J", "initials": "NJ", "orcid": "0000-0001-9283-9978", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/705d15d93d6c4a06bcfec8fad5941a9d.json"}}, {"family": "Nordlund", "given": "P\u00e4r", "initials": "P"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Wiman", "given": "Klas G", "initials": "KG", "orcid": "0000-0002-7113-524X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/536683a931c44e32aa475e97f696e4ba.json"}}], "type": "journal article", "published": "2021-07-15", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "12", "issue": "7", "pages": "709", "issn-l": "2041-4889"}, "abstract": "Asparaginase depletes extracellular asparagine in the blood and is an important treatment for acute lymphoblastic leukemia (ALL) due to asparagine auxotrophy of ALL blasts. Unfortunately, resistance occurs and has been linked to expression of the enzyme asparagine synthetase (ASNS), which generates asparagine from intracellular sources. Although TP53 is the most frequently mutated gene in cancer overall, TP53 mutations are rare in ALL. However, TP53 mutation is associated with poor therapy response and occurs at higher frequency in relapsed ALL. The mutant p53-reactivating compound APR-246 (Eprenetapopt/PRIMA-1Met) is currently being tested in phase II and III clinical trials in several hematological malignancies with mutant TP53. Here we present CEllular Thermal Shift Assay (CETSA) data indicating that ASNS is a direct or indirect target of APR-246 via the active product methylene quinuclidinone (MQ). Furthermore, combination treatment with asparaginase and APR-246 resulted in synergistic growth suppression in ALL cell lines. Our results thus suggest a potential novel treatment strategy for ALL.", "doi": "10.1038/s41419-021-03988-y", "pmid": "34267184", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8282662"}, {"db": "pii", "key": "10.1038/s41419-021-03988-y"}], "notes": [], "created": "2026-08-20T08:49:42.200Z", "modified": "2026-08-20T08:49:42.515Z"}, {"entity": "publication", "iuid": "87f70f40c84e446fbf7a2043a5a6fcfb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/87f70f40c84e446fbf7a2043a5a6fcfb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/87f70f40c84e446fbf7a2043a5a6fcfb"}}, "title": "Drug synergy scoring using minimal dose response matrices.", "authors": [{"family": "M\u00e4kel\u00e4", "given": "Petri", "initials": "P"}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2021-01-19", "journal": {"title": "BMC Res Notes", "issn": "1756-0500", "volume": "14", "issue": "1", "pages": "27", "issn-l": null}, "abstract": "Combinations of pharmacological agents are essential for disease control and prevention, offering many advantages over monotherapies, with one of these being drug synergy. The state-of-the-art method to profile drug synergy in preclinical research is by using dose-response matrices in disease-appropriate models, however this approach is frequently labour intensive and cost-ineffective, particularly when performed in a medium- to high-throughput fashion. Thus, in this study, we set out to optimise a parameter of this methodology, determining the minimal matrix size that can be used to robustly detect and quantify synergy between two drugs.\n\nWe used a drug matrix reduction workflow that allowed the identification of a minimal drug matrix capable of robustly detecting and quantifying drug synergy. These minimal matrices utilise substantially less reagents and data processing power than their typically used larger counterparts. Focusing on the antileukemic efficacy of the chemotherapy combination of cytarabine and inhibitors of ribonucleotide reductase, we could show that detection and quantification of drug synergy by three common synergy models was well-tolerated despite reducing matrix size from 8 \u00d7 8 to 4 \u00d7 4. Overall, the optimisation of drug synergy scoring as presented here could inform future medium- to high-throughput drug synergy screening strategies in pre-clinical research.", "doi": "10.1186/s13104-021-05445-7", "pmid": "33468238", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7816329"}, {"db": "pii", "key": "10.1186/s13104-021-05445-7"}], "notes": [], "created": "2026-08-20T12:22:10.206Z", "modified": "2026-08-20T12:22:10.316Z"}, {"entity": "publication", "iuid": "4cca1508c6224caa8a80b4105099e6b8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4cca1508c6224caa8a80b4105099e6b8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4cca1508c6224caa8a80b4105099e6b8"}}, "title": "Drug synergy scoring using minimal dose response matrices", "authors": [{"family": "M\u00e4kel\u00e4", "given": "Petri", "initials": "P"}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "posted-content", "published": "2020-10-31", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.10.30.362103", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:59:38.568Z", "modified": "2026-08-20T09:59:58.034Z"}, {"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": "4d5ffd4af8f14e078dba8ddfbb547cdd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4d5ffd4af8f14e078dba8ddfbb547cdd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4d5ffd4af8f14e078dba8ddfbb547cdd"}}, "title": "SAMHD1 promotes oncogene-induced replication stress", "authors": [{"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Calder\u00f3n-Monta\u00f1o", "given": "Jose M", "initials": "JM", "orcid": "0000-0001-6845-797X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06bf2684da93449381c951c32dc14703.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "posted-content", "published": "2020-07-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.07.29.226282", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:58:29.509Z", "modified": "2026-08-20T09:58:29.595Z"}, {"entity": "publication", "iuid": "21611b7320444c8c91a281142f2b7510", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/21611b7320444c8c91a281142f2b7510.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/21611b7320444c8c91a281142f2b7510"}}, "title": "Author Correction: Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.", "authors": [{"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48bb9c8ab8a5465a8a4da1997f1af56d.json"}}, {"family": "Wright", "given": "Roni H G", "initials": "RHG"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Isaksson", "given": "Rebecka", "initials": "R"}, {"family": "Carter", "given": "Megan", "initials": "M"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Font-Mateu", "given": "Jofre", "initials": "J"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S", "orcid": "0000-0003-3187-722X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f303f034442346a18e9e57e6b5cd2ae0.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P"}, {"family": "Jeppsson", "given": "Fredrik", "initials": "F"}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Almqvist", "given": "Helena", "initials": "H"}, {"family": "Axelsson", "given": "Hanna", "initials": "H"}, {"family": "Regmi", "given": "Shruti", "initials": "S"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "AL"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}, {"family": "Beato", "given": "Miguel", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}], "type": "published erratum", "published": "2019-11-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "10", "issue": "1", "pages": "5050", "issn-l": "2041-1723"}, "abstract": "An amendment to this paper has been published and can be accessed via a link at the top of the paper.", "doi": "10.1038/s41467-019-12806-1", "pmid": "31676755", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6825185"}, {"db": "pii", "key": "10.1038/s41467-019-12806-1"}], "notes": [], "created": "2026-08-20T08:50:42.836Z", "modified": "2026-08-20T08:50:42.966Z"}, {"entity": "publication", "iuid": "565c8ebd51d44e2ebe08d32f106f0c85", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/565c8ebd51d44e2ebe08d32f106f0c85.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/565c8ebd51d44e2ebe08d32f106f0c85"}}, "title": "MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells", "authors": [{"family": "Gad", "given": "Helge", "initials": "H"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Stolz", "given": "Ailine", "initials": "A", "orcid": "0000-0002-1051-7527", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd53f689f44b4e8b928ebe2e77f41999.json"}}, {"family": "Amaral", "given": "Nuno", "initials": "N"}, {"family": "Brautigham", "given": "Lars", "initials": "L"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Kald\u00e9ren", "given": "Christina", "initials": "C"}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Visnes", "given": "Torkild", "initials": "T"}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Calderon Montano", "given": "Jos\u00e9 Manuel", "initials": "JM"}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Groth", "given": "Petra", "initials": "P"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Gokturk", "given": "Camilla", "initials": "C"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Wakchaure", "given": "Prasad", "initials": "P"}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Bastians", "given": "Holger", "initials": "H"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"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": "2019-03-12", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/575290", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:10.066Z", "modified": "2026-08-20T11:13:10.124Z"}, {"entity": "publication", "iuid": "b4db075ab70943f285667735e4f0a1bf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b4db075ab70943f285667735e4f0a1bf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b4db075ab70943f285667735e4f0a1bf"}}, "title": "MTH1 inhibitor TH588 induces mitosis-dependent accumulation of genomic 8-oxodG and disturbs mitotic progression", "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": "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"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"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": "2019-03-12", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/573931", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:08.309Z", "modified": "2026-08-20T11:13:08.364Z"}, {"entity": "publication", "iuid": "64004c6537984d5fa5d1b075c7cbf09a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/64004c6537984d5fa5d1b075c7cbf09a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/64004c6537984d5fa5d1b075c7cbf09a"}}, "title": "Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens.", "authors": [{"family": "Rassidakis", "given": "George Z", "initials": "GZ"}, {"family": "Herold", "given": "Nikolas", "initials": "N"}, {"family": "Myrberg", "given": "Ida Hed", "initials": "IH"}, {"family": "Tsesmetzis", "given": "Nikolaos", "initials": "N"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Henter", "given": "Jan-Inge", "initials": "JI"}, {"family": "Schaller", "given": "Torsten", "initials": "T"}, {"family": "Ng", "given": "Siok-Bian", "initials": "SB"}, {"family": "Chng", "given": "Wee Joo", "initials": "WJ"}, {"family": "Yan", "given": "Benedict", "initials": "B"}, {"family": "Ng", "given": "Chin Hin", "initials": "CH"}, {"family": "Ravandi", "given": "Farhad", "initials": "F"}, {"family": "Andreeff", "given": "Michael", "initials": "M"}, {"family": "Kantarjian", "given": "Hagop M", "initials": "HM"}, {"family": "Medeiros", "given": "L Jeffrey", "initials": "LJ"}, {"family": "Xagoraris", "given": "Ioanna", "initials": "I"}, {"family": "Khoury", "given": "Joseph D", "initials": "JD", "orcid": "0000-0003-2621-3584", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21ea62030f82471e81b85b5e78829ae1.json"}}], "type": "journal article", "published": "2018-10-19", "journal": {"title": "Blood Cancer J", "issn": "2044-5385", "volume": "8", "issue": "11", "pages": "98", "issn-l": null}, "abstract": "Sterile alpha motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) limits the efficacy of cytarabine (ara-C) used in AML by hydrolyzing its active metabolite ara-CTP and thus represents a promising therapeutic target. SAMHD1 has also been implicated in DNA damage repair that may impact DNA damage-inducing therapies such as anthracyclines, during induction therapy. To determine whether SAMHD1 limits ara-C efficacy during induction or consolidation therapy, SAMHD1 protein levels were assessed in two patient cohorts of de novo AML from The University of Texas MD Anderson Cancer Center (USA) and the National University Hospital (Singapore), respectively, using immunohistochemistry and tissue microarrays. SAMHD1 was expressed at a variable level by AML blasts but not in a broad range of normal hematopoietic cells in reactive bone marrows. A sizeable patient subset with low SAMHD1 expression (<25% of positive blasts) was identified, which was significantly associated with longer event-free (EFS) and overall (OS) survival in patients receiving high-dose cytarabine (HDAC) during consolidation. Therefore, evaluation of SAMHD1 expression level in AML blasts at diagnosis, may stratify patient groups for future clinical trials combining HDAC with novel SAMHD1 inhibitors as consolidation therapy.", "doi": "10.1038/s41408-018-0134-z", "pmid": "30341277", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6195559"}, {"db": "pii", "key": "10.1038/s41408-018-0134-z"}], "notes": [], "created": "2026-08-20T08:49:02.357Z", "modified": "2026-08-20T08:49:02.442Z"}, {"entity": "publication", "iuid": "ad8c0e59f9c1458793d5a1182228a464", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ad8c0e59f9c1458793d5a1182228a464.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ad8c0e59f9c1458793d5a1182228a464"}}, "title": "Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism.", "authors": [{"family": "Tsesmetzis", "given": "Nikolaos", "initials": "N"}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}], "type": "journal article", "published": "2018-07-23", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "10", "issue": "7", "issn-l": "2072-6694"}, "abstract": "Antimetabolites, in particular nucleobase and nucleoside analogues, are cytotoxic drugs that, starting from the small field of paediatric oncology, in combination with other chemotherapeutics, have revolutionised clinical oncology and transformed cancer into a curable disease. However, even though combination chemotherapy, together with radiation, surgery and immunotherapy, can nowadays cure almost all types of cancer, we still fail to achieve this for a substantial proportion of patients. The understanding of differences in metabolism, pharmacokinetics, pharmacodynamics, and tumour biology between patients that can be cured and patients that cannot, builds the scientific basis for rational therapy improvements. Here, we summarise current knowledge of how tumour-specific and patient-specific factors can dictate resistance to nucleobase/nucleoside analogues, and which strategies of re-sensitisation exist. We revisit well-established hurdles to treatment efficacy, like the blood-brain barrier and reduced deoxycytidine kinase activity, but will also discuss the role of novel resistance factors, such as SAMHD1. A comprehensive appreciation of the complex mechanisms that underpin the failure of chemotherapy will hopefully inform future strategies of personalised medicine.", "doi": "10.3390/cancers10070240", "pmid": "30041457", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6071274"}, {"db": "pii", "key": "cancers10070240"}], "notes": [], "created": "2026-08-20T13:39:10.206Z", "modified": "2026-08-20T13:39:10.275Z"}, {"entity": "publication", "iuid": "239b778e2e954ecf8a5d32bbc4735453", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/239b778e2e954ecf8a5d32bbc4735453.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/239b778e2e954ecf8a5d32bbc4735453"}}, "title": "SAMHD1 is a barrier to antimetabolite-based cancer therapies.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93d3003ec7854be68f4e38283bca1da0.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}], "type": "journal article", "published": "2017-02-03", "journal": {"title": "Mol Cell Oncol", "issn": "2372-3556", "volume": "4", "issue": "2", "pages": "e1287554", "issn-l": null}, "abstract": "The outcome of acute myelogenous leukemia (AML) therapy depends on the propensity of leukemic blasts to accumulate ara-CTP, the active triphosphate of cytarabine (ara-C). We identified sterile \u03b1 motif and HD domain-containing protein 1 (SAMHD1) as an ara-CTPase that protects cancer cells from cytarabine-induced toxicity. Therefore, we propose targeting SAMHD1 as a strategy to potentiate cytarabine and possibly other antimetabolite-based therapies.", "doi": "10.1080/23723556.2017.1287554", "pmid": "28401188", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5383367"}, {"db": "pii", "key": "1287554"}], "notes": [], "created": "2026-08-20T09:37:44.566Z", "modified": "2026-08-20T09:37:44.676Z"}]}