{"entity": "researcher", "timestamp": "2026-07-11T14:31:51.231Z", "family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "affiliations": ["Department of Laboratory Medicine, Translational Cancer Research, Lund University Cancer Center, Lund University, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1"}}, "publications": [{"entity": "publication", "iuid": "7168698f97694d46ba7aae5af6601e25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7168698f97694d46ba7aae5af6601e25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7168698f97694d46ba7aae5af6601e25"}}, "title": "Evaluation of TRPA1 as a Therapeutic Target in MYCN-Amplified Neuroblastoma.", "authors": [{"family": "Seger", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-3191-5302", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfcd0a0a226c417eac8e0a48eedd4e7c.json"}}, {"family": "Adami\u010d", "given": "Dora", "initials": "D"}, {"family": "Olmos", "given": "Erick Muci\u00f1o", "initials": "EM"}, {"family": "Nilsson", "given": "Johannes", "initials": "J", "orcid": "0009-0004-3976-526X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1c6ff03f6da452e9bb867a959d84ab8.json"}}, {"family": "Granados-Aparici", "given": "Sofia", "initials": "S"}, {"family": "Vieco-Marti", "given": "Isaac", "initials": "I"}, {"family": "Esfandyari", "given": "Javanshir", "initials": "J"}, {"family": "Engstr\u00f6m", "given": "Matilda", "initials": "M"}, {"family": "Martinez", "given": "Julia", "initials": "J", "orcid": "0009-0004-4050-8439", "researcher": {"href": "https://publications.scilifelab.se/researcher/702e1de02611472097fd90ea328a0630.json"}}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Navarro", "given": "Samuel", "initials": "S"}, {"family": "Noguera", "given": "Rosa", "initials": "R"}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Pediatr Blood Cancer", "issn": "1545-5017", "volume": "72", "issue": "9", "pages": "e31875", "issn-l": "1545-5009"}, "abstract": "Neuroblastoma (NB) is a childhood cancer with a high relapse rate despite intensive treatment. TRPA1 is a pain-sensing ion channel with downstream impacts on proliferative and pro-apoptotic pathways. Here, we evaluated TRPA1 expression in NB and performed pharmacological inhibition in preclinical models to assess its potential as a therapeutic target in NB.\n\nTRPA1 protein levels were assessed in NB patient tumors on tissue microarrays. Bulk and single-cell gene expression data were retrieved from publicly available databases. The effects of three TRPA1 inhibitors (AP-18, A967079, and Bay 390) on NB cell viability and cell death were evaluated using NB patient-derived xenograft (PDX)-derived organoids. In vivo testing was performed in a MYCN-amplified NB PDX model. Drug combination testing was performed using combination or sequential treatments and evaluated using drug synergy scores.\n\nTRPA1 is widely expressed in NB patient tumors and preclinical patient-derived NB models. Pharmacological TRPA1 inhibition decreased NB cell viability and increased cell death. In vivo TRPA1 inhibition alone did not significantly affect NB tumor growth. Pretreatment with TRPA1 inhibition prior to chemotherapy resulted in synergistic effects in vitro.\n\nTRPA1 is expressed in NB tumors, and pharmacological TRPA1 inhibition can be effective in vitro and synergistic when used as pretreatment to chemotherapy. However, the tested inhibitors did not show in vivo efficacy, at least as monotherapy.", "doi": "10.1002/pbc.31875", "pmid": "40556352", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-28T10:40:42.039Z", "modified": "2025-11-28T10:40:42.266Z"}, {"entity": "publication", "iuid": "2424a9f7eb5c4b9f85690b0af2c8405e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2424a9f7eb5c4b9f85690b0af2c8405e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2424a9f7eb5c4b9f85690b0af2c8405e"}}, "title": "Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma.", "authors": [{"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Yasui", "given": "Hiroaki", "initials": "H"}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Jansson", "given": "Caroline", "initials": "C"}, {"family": "Durand", "given": "Geoffroy", "initials": "G"}, {"family": "Ravi", "given": "Naveen", "initials": "N"}, {"family": "Ferro", "given": "Michele", "initials": "M"}, {"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications.scilifelab.se/researcher/62822d0b9c6c4a01a53829b9b05443ba.json"}}, {"family": "Chattopadhyay", "given": "Subhayan", "initials": "S"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}, {"family": "Spierings", "given": "Diana", "initials": "D", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Valind", "given": "Anders", "initials": "A", "orcid": "0000-0002-1654-6978", "researcher": {"href": "https://publications.scilifelab.se/researcher/08f05da015554b19852439d14cb8e99b.json"}}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}], "type": "journal article", "published": "2024-10-18", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "8992", "issn-l": "2041-1723"}, "abstract": "Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.", "doi": "10.1038/s41467-024-53334-x", "pmid": "39419962", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11486966"}, {"db": "pii", "key": "10.1038/s41467-024-53334-x"}], "notes": [], "created": "2024-11-14T09:28:32.271Z", "modified": "2024-11-17T16:43:33.354Z"}, {"entity": "publication", "iuid": "ed05b16509414bc8b557611000e36d26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed05b16509414bc8b557611000e36d26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed05b16509414bc8b557611000e36d26"}}, "title": "Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance.", "authors": [{"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Adamska", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-7152-4149", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f2fab5686a542fdb1286417685bc7a4.json"}}, {"family": "Seger", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-3191-5302", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfcd0a0a226c417eac8e0a48eedd4e7c.json"}}, {"family": "Yasui", "given": "Hiroaki", "initials": "H"}, {"family": "van den Bos", "given": "Hilda", "initials": "H", "orcid": "0000-0001-9787-8597", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3f0fd58a2714db5bcd89642f92c0158.json"}}, {"family": "Radke", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-4460-0812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad483c946ce244fa898cadb6238e970d.json"}}, {"family": "Esfandyari", "given": "Javanshir", "initials": "J"}, {"family": "Bhave", "given": "Madhura Satish", "initials": "MS"}, {"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Spierings", "given": "Diana", "initials": "D", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2022-10-28", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "8", "issue": "43", "pages": "eabq4617", "issn-l": "2375-2548"}, "abstract": "Chemotherapy resistance and relapses are common in high-risk neuroblastoma (NB). Here, we developed a clinically relevant in vivo treatment protocol mimicking the first-line five-chemotherapy treatment regimen of high-risk NB and applied this protocol to mice with MYCN-amplified NB patient-derived xenografts (PDXs). Genomic and transcriptomic analyses were used to reveal NB chemoresistance mechanisms. Intrinsic resistance was associated with high genetic diversity and an embryonic phenotype. Relapsed NB with acquired resistance showed a decreased adrenergic phenotype and an enhanced immature mesenchymal-like phenotype, resembling multipotent Schwann cell precursors. NBs with a favorable treatment response presented a lineage-committed adrenergic phenotype similar to normal neuroblasts. Novel integrated phenotypic gene signatures reflected treatment response and patient prognosis. NB organoids established from relapsed PDX tumors retained drug resistance, tumorigenicity, and transcriptional cell states. This work sheds light on the mechanisms of NB chemotherapy response and emphasizes the importance of transcriptional cell states in chemoresistance.", "doi": "10.1126/sciadv.abq4617", "pmid": "36306349", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9616506"}], "notes": [], "created": "2022-11-15T12:56:52.046Z", "modified": "2023-06-01T06:43:02.747Z"}, {"entity": "publication", "iuid": "33c3ddf5a31f4f7cadbc0051c14e7d45", "links": {"self": {"href": "https://publications.scilifelab.se/publication/33c3ddf5a31f4f7cadbc0051c14e7d45.json"}, "display": {"href": "https://publications.scilifelab.se/publication/33c3ddf5a31f4f7cadbc0051c14e7d45"}}, "title": "Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis.", "authors": [{"family": "Grigoryan", "given": "Ani", "initials": "A", "orcid": "0000-0003-2757-7021", "researcher": {"href": "https://publications.scilifelab.se/researcher/071b6f9344cb4f479fbb0cd48393ce87.json"}}, {"family": "Zacharaki", "given": "Dimitra", "initials": "D", "orcid": "0000-0003-4954-233X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e82fb25f7124c0eab3ad721cc123554.json"}}, {"family": "Balhuizen", "given": "Alexander", "initials": "A", "orcid": "0000-0001-7581-121X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a95edbcd57d43a0a7436700d678a31c.json"}}, {"family": "C\u00f4me", "given": "Christophe Rm", "initials": "CR", "orcid": "0000-0001-5229-4440", "researcher": {"href": "https://publications.scilifelab.se/researcher/270e78a4eb244edc8115d4f52c439b67.json"}}, {"family": "Garcia", "given": "Alejandro Garcia", "initials": "AG", "orcid": "0000-0002-7358-7004", "researcher": {"href": "https://publications.scilifelab.se/researcher/757ba644689b44c9b24fa489fec62dc4.json"}}, {"family": "Hidalgo Gil", "given": "David", "initials": "D", "orcid": "0000-0002-9345-652X", "researcher": {"href": "https://publications.scilifelab.se/researcher/14c691526f634c4483c1db6f44079fa4.json"}}, {"family": "Frank", "given": "Anne-Katrine", "initials": "AK"}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Esfandyari", "given": "Javanshir", "initials": "J"}, {"family": "Kjellman", "given": "Pontus", "initials": "P"}, {"family": "Englund", "given": "Emelie", "initials": "E"}, {"family": "Rodriguez", "given": "Carmen", "initials": "C", "orcid": "0000-0003-3611-2496", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc21fda46821483eb954ffe9c05158b1.json"}}, {"family": "Sime", "given": "Wondossen", "initials": "W", "orcid": "0000-0001-9518-2457", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b1353a0ded04eb88c564117345c556f.json"}}, {"family": "Massoumi", "given": "Ramin", "initials": "R", "orcid": "0000-0001-8875-6440", "researcher": {"href": "https://publications.scilifelab.se/researcher/c019a5eed3144760b8c55badc75280f7.json"}}, {"family": "Kalantari", "given": "Nasim", "initials": "N", "orcid": "0000-0002-8619-3936", "researcher": {"href": "https://publications.scilifelab.se/researcher/d23dd9f622c0459b8cfd0064ee7511e2.json"}}, {"family": "Prithiviraj", "given": "Sujeethkumar", "initials": "S"}, {"family": "Li", "given": "Yuan", "initials": "Y"}, {"family": "Dupard", "given": "Steven J", "initials": "SJ", "orcid": "0000-0003-1762-746X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef9ce529bbbf434f945efbc71dcba327.json"}}, {"family": "Isaksson", "given": "Hanna", "initials": "H", "orcid": "0000-0002-9690-8907", "researcher": {"href": "https://publications.scilifelab.se/researcher/3346ac999b834952b56814f654016446.json"}}, {"family": "Madsen", "given": "Chris D", "initials": "CD", "orcid": "0000-0001-6838-2103", "researcher": {"href": "https://publications.scilifelab.se/researcher/466f82bcf9364350a22cd7d3be0833e4.json"}}, {"family": "Porse", "given": "Bo T", "initials": "BT", "orcid": "0000-0001-6043-0844", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd4987da02c24b2eab98db3f71e06751.json"}}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}, {"family": "Bourgine", "given": "Paul E", "initials": "PE", "orcid": "0000-0002-7639-6844", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1457096ac494b2581f115b45e9a13b0.json"}}], "type": "journal article", "published": "2022-10-12", "journal": {"title": "Sci Transl Med", "issn": "1946-6242", "volume": "14", "issue": "666", "pages": "eabm6391", "issn-l": "1946-6234"}, "abstract": "The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude the human-specific functional interactions of stem cells with their bone marrow microenvironment. Instead, human mesenchymal cells can be exploited for the in vivo engineering of humanized niches, which confer robust engraftment of human healthy and malignant blood samples. However, mesenchymal cells are associated with major reproducibility issues in tissue formation. Here, we report the fast and standardized generation of human mini-bones by a custom-designed human mesenchymal cell line. These resulting humanized ossicles (hOss) consist of fully mature bone and bone marrow structures hosting a human mesenchymal niche with retained stem cell properties. As compared to mouse bones, we demonstrate superior engraftment of human cord blood hematopoietic cells and primary acute myeloid leukemia samples and also validate hOss as a metastatic site for breast cancer cells. We further report the engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically described osteolytic lesions. Collectively, our human mini-bones constitute a powerful preclinical platform to model bone-developing tumors using patient-derived materials.", "doi": "10.1126/scitranslmed.abm6391", "pmid": "36223446", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2022-11-29T07:57:46.468Z", "modified": "2023-02-20T13:52:55.809Z"}, {"entity": "publication", "iuid": "93a54b75e2294c589b968a9de83166e9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93a54b75e2294c589b968a9de83166e9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93a54b75e2294c589b968a9de83166e9"}}, "title": "Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma.", "authors": [{"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Radke", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-4460-0812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad483c946ce244fa898cadb6238e970d.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Saarela", "given": "Jani", "initials": "J", "orcid": "0000-0001-7306-7175", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5febb7d8bc04ecb9664e3be19f4bb37.json"}}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Sj\u00f6lund", "given": "Jonas", "initials": "J", "orcid": "0000-0002-6992-3415", "researcher": {"href": "https://publications.scilifelab.se/researcher/eccac6b320244409879d5bac740f5202.json"}}, {"family": "Smith", "given": "Emma M", "initials": "EM", "orcid": "0000-0003-0609-4864", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b453bd8533f4359b50e71c5aafa3d2a.json"}}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications.scilifelab.se/researcher/5be0a3ec07654822a91df964eab1d6e4.json"}}, {"family": "P\u00e5hlman", "given": "Sven", "initials": "S"}, {"family": "Wennerberg", "given": "Krister", "initials": "K", "orcid": "0000-0002-1352-4220", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a447e220e144c63a907f9c824ccc9da.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2020-09-23", "journal": {"title": "Sci Transl Med", "issn": "1946-6242", "volume": "12", "issue": "562", "issn-l": "1946-6234"}, "abstract": "Neuroblastoma is a childhood malignancy with often dismal prognosis; relapse is common despite intense treatment. Here, we used human tumor organoids representing multiple MYCN-amplified high-risk neuroblastomas to perform a high-throughput drug screen with approved or emerging oncology drugs. Tumor-selective effects were calculated using drug sensitivity scores. Several drugs with previously unreported anti-neuroblastoma effects were identified by stringent selection criteria. ARRY-520, an inhibitor of kinesin spindle protein (KSP), was among those causing reduced viability. High expression of the KSP-encoding gene KIF11 was associated with poor outcome in neuroblastoma. Genome-scale loss-of-function screens in hundreds of human cancer cell lines across 22 tumor types revealed that KIF11 is particularly important for neuroblastoma cell viability. KSP inhibition in neuroblastoma patient-derived xenograft (PDX) cells resulted in the formation of abnormal monoastral spindles, mitotic arrest, up-regulation of mitosis-associated genes, and apoptosis. In vivo, KSP inhibition caused regression of MYCN-amplified neuroblastoma PDX tumors. Furthermore, treatment of mice harboring orthotopic neuroblastoma PDX tumors resulted in increased survival. Our results suggested that KSP inhibition could be a promising treatment strategy in children with high-risk neuroblastoma.", "doi": "10.1126/scitranslmed.aba4434", "pmid": "32967973", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "12/562/eaba4434"}], "notes": [], "created": "2021-11-24T07:56:38.972Z", "modified": "2021-11-24T07:56:39.291Z"}, {"entity": "publication", "iuid": "9b592e44470a4ba18b57b727b2011b71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9b592e44470a4ba18b57b727b2011b71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9b592e44470a4ba18b57b727b2011b71"}}, "title": "Integrative discovery of treatments for high-risk neuroblastoma.", "authors": [{"family": "Almstedt", "given": "Elin", "initials": "E", "orcid": "0000-0002-1946-9138", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4414ac7f9284bf9bf0b52530ec19ee3.json"}}, {"family": "Elgendy", "given": "Ramy", "initials": "R", "orcid": "0000-0002-2592-3448", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a5ce4db4317446bb1ef113f7c6e8eb5.json"}}, {"family": "Hekmati", "given": "Neda", "initials": "N"}, {"family": "Ros\u00e9n", "given": "Emil", "initials": "E", "orcid": "0000-0002-1664-2257", "researcher": {"href": "https://publications.scilifelab.se/researcher/db0751a3a95e488bb849059c09c4fc7d.json"}}, {"family": "W\u00e4rn", "given": "Caroline", "initials": "C"}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK"}, {"family": "Dyberg", "given": "Cecilia", "initials": "C"}, {"family": "Doroszko", "given": "Milena", "initials": "M"}, {"family": "Larsson", "given": "Ida", "initials": "I", "orcid": "0000-0001-5422-4243", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac604ca793048e9b6ddaa3459b4e97a.json"}}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Arsenian Henriksson", "given": "Marie", "initials": "M"}, {"family": "P\u00e5hlman", "given": "Sven", "initials": "S"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M", "orcid": "0000-0002-0709-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa2148fbafb44d59bd110e36bd77769c.json"}}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "J\u00f6rnsten", "given": "Rebecka", "initials": "R"}, {"family": "Krona", "given": "Cecilia", "initials": "C"}, {"family": "Nelander", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2020-01-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "71"}, "abstract": "Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.", "doi": "10.1038/s41467-019-13817-8", "pmid": "31900415", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-13817-8"}, {"db": "pmc", "key": "PMC6941971"}], "notes": [], "created": "2020-01-08T11:24:16.666Z", "modified": "2021-12-09T14:05:49.139Z"}, {"entity": "publication", "iuid": "0f2331aa611d42ee9f36a6feae028efa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f2331aa611d42ee9f36a6feae028efa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f2331aa611d42ee9f36a6feae028efa"}}, "title": "Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.", "authors": [{"family": "Mohlin", "given": "Sofie", "initials": "S", "orcid": "0000-0002-2458-3963", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e095a99e2c84d52b13973c9d46d128a.json"}}, {"family": "Hansson", "given": "Karin", "initials": "K"}, {"family": "Radke", "given": "Katarzyna", "initials": "K"}, {"family": "Martinez", "given": "Sonia", "initials": "S", "orcid": "0000-0003-2230-7794", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8f2d7aabe8e4b24b58846c7a45c48fa.json"}}, {"family": "Blanco-Apiricio", "given": "Carmen", "initials": "C"}, {"family": "Garcia-Ruiz", "given": "Cristian", "initials": "C", "orcid": "0000-0003-2914-7914", "researcher": {"href": "https://publications.scilifelab.se/researcher/07826d677ce449e2811d69e273becfb4.json"}}, {"family": "Welinder", "given": "Charlotte", "initials": "C"}, {"family": "Esfandyari", "given": "Javanshir", "initials": "J"}, {"family": "O'Neill", "given": "Michael", "initials": "M"}, {"family": "Pastor", "given": "Joaquin", "initials": "J"}, {"family": "von Stedingk", "given": "Kristoffer", "initials": "K"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2019-08-00", "journal": {"title": "EMBO Mol Med", "issn": "1757-4684", "issn-l": "1757-4676", "volume": "11", "issue": "8", "pages": "e10058"}, "abstract": "The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma.", "doi": "10.15252/emmm.201810058", "pmid": "31310053", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Structural Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6685085"}, {"db": "GEO", "key": "GSE133137"}], "notes": [], "created": "2019-11-25T15:10:57.025Z", "modified": "2021-07-07T08:25:36.622Z"}]}