{"entity": "researcher", "timestamp": "2026-08-07T19:31:13.295Z", "family": "Seger", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-3191-5302", "affiliations": ["Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22381, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/dfcd0a0a226c417eac8e0a48eedd4e7c.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/dfcd0a0a226c417eac8e0a48eedd4e7c"}}, "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": "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"}]}