{"entity": "journal", "iuid": "db0b159104bd48d794da94ca6f4d3839", "timestamp": "2026-09-03T05:14:47.142Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Lung%20Cancer.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Lung%20Cancer"}}, "title": "Lung Cancer", "issn": "1872-8332", "issn-l": null, "publications_count": 3, "publications": [{"entity": "publication", "iuid": "1c2c1a8b1e084b91a7a81f55add3ed39", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1c2c1a8b1e084b91a7a81f55add3ed39.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1c2c1a8b1e084b91a7a81f55add3ed39"}}, "title": "Novel therapeutic approaches for pleural mesothelioma identified by functional ex vivo drug sensitivity testing.", "authors": [{"family": "Ollila-Raj", "given": "Hely", "initials": "H"}, {"family": "Murum\u00e4gi", "given": "Astrid", "initials": "A"}, {"family": "Pellinen", "given": "Teijo", "initials": "T"}, {"family": "Arjama", "given": "Mariliina", "initials": "M"}, {"family": "Sutinen", "given": "Eva", "initials": "E"}, {"family": "Volmonen", "given": "Kirsi", "initials": "K"}, {"family": "Haikala", "given": "Heidi M", "initials": "HM"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}, {"family": "M\u00e4yr\u00e4np\u00e4\u00e4", "given": "Mikko I", "initials": "MI"}, {"family": "Ilonen", "given": "Ilkka", "initials": "I"}], "type": "journal article", "published": "2023-04-00", "journal": {"title": "Lung Cancer", "issn": "1872-8332", "volume": "178", "pages": "213-219", "issn-l": null}, "abstract": "Pleural mesothelioma (PM) is an aggressive malignancy with limited treatment options. The first-line therapy has remained unchanged for two decades and consists of pemetrexed in combination with cisplatin. Immune-checkpoint inhibitors (nivolumab plus ipilimumab) have high response rates, resulting in recent updates in treatment recommendations by the U.S. Food and Drug Administration. However, the overall benefits of combination treatment are modest, suggesting that other targeted therapy options should be investigated.\n\nWe employed high-throughput drug sensitivity and resistance testing on five established PM cell lines using 527 cancer drugs in a 2D setting. Drugs of the greatest potential (n = 19) were selected for further testing in primary cell models derived from pleural effusions of seven PM patients.\n\nAll established and primary patient-derived PM cell models were sensitive to the mTOR inhibitor AZD8055. Furthermore, another mTOR inhibitor (temsirolimus) showed efficacy in most of the primary patient-derived cells, although a less robust effect was observed when compared with the established cell lines. Most of the established cell lines and all patient-derived primary cells exhibited sensitivity to the PI3K/mTOR/DNA-PK inhibitor LY3023414. The Chk1 inhibitor prexasertib showed activity in 4/5 (80%) of the established cell lines and in 2/7 (29%) of the patient-derived primary cell lines. The BET family inhibitor JQ1 showed activity in four patient-derived cell models and in one established cell line.\n\nmTOR and Chk1 pathways had promising results with established mesothelioma cell lines in an ex vivo setting. In patient-derived primary cells, drugs targeting mTOR pathway in particular showed efficacy. These findings may inform novel treatment strategies for PM.", "doi": "10.1016/j.lungcan.2023.02.024", "pmid": "36878102", "labels": [], "xrefs": [{"db": "pii", "key": "S0169-5002(23)00085-5"}], "notes": [], "created": "2026-08-20T08:00:23.489Z", "modified": "2026-08-20T08:00:23.557Z"}, {"entity": "publication", "iuid": "f01a55099bb6470f88f21ac5051105fc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f01a55099bb6470f88f21ac5051105fc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f01a55099bb6470f88f21ac5051105fc"}}, "title": "Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation.", "authors": [{"family": "Moreno-Ruiz", "given": "Pablo", "initials": "P"}, {"family": "Corvigno", "given": "Sara", "initials": "S"}, {"family": "Te Grootenhuis", "given": "Nienke C", "initials": "NC"}, {"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Backman", "given": "Max", "initials": "M"}, {"family": "Strell", "given": "Carina", "initials": "C"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Hoelzlwimmer", "given": "Gabriele", "initials": "G"}, {"family": "Klein", "given": "Christian", "initials": "C"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "\u00d6stman", "given": "Arne", "initials": "A"}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "Lung Cancer", "issn": "1872-8332", "volume": "155", "pages": "10-19", "issn-l": null}, "abstract": "Fibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGF\u03b2R and \u03b1-SMA fibroblast markers in a well-annotated clinical cohort of non-small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival.\n\nA well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGF\u03b2R and \u03b1-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients.\n\nHigh stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012-2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126-2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. \u03b1-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high \u03b1-SMA (p = 0.003) and FAP expression (p < 0.001).\n\nThe study identifies FAP intensity as a candidate independent NSCLC prognostic biomarker. The study also suggests continued analyses of the relationships between genetic driver mutations and the composition of tumor stroma, as well as continued probing of marker-defined fibroblasts as NSCLC subset-specific modifiers of immune surveillance and outcome.", "doi": "10.1016/j.lungcan.2021.02.028", "pmid": "33706022", "labels": [], "xrefs": [{"db": "pii", "key": "S0169-5002(21)00088-X"}], "notes": [], "created": "2026-08-21T11:24:48.877Z", "modified": "2026-08-21T11:24:48.902Z"}, {"entity": "publication", "iuid": "155d2fcbbe284e3da14a659c64080fc2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/155d2fcbbe284e3da14a659c64080fc2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/155d2fcbbe284e3da14a659c64080fc2"}}, "title": "The evolving landscape of biomarker testing for non-small cell lung cancer in Europe.", "authors": [{"family": "Kerr", "given": "Keith M", "initials": "KM"}, {"family": "Bibeau", "given": "Fr\u00e9d\u00e9ric", "initials": "F"}, {"family": "Thunnissen", "given": "Erik", "initials": "E"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ry\u0161ka", "given": "Ale\u0161", "initials": "A"}, {"family": "Wolf", "given": "J\u00fcrgen", "initials": "J"}, {"family": "\u00d6hrling", "given": "Katarina", "initials": "K"}, {"family": "Burdon", "given": "Peter", "initials": "P"}, {"family": "Malapelle", "given": "Umberto", "initials": "U"}, {"family": "B\u00fcttner", "given": "Reinhard", "initials": "R"}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Lung Cancer", "issn": "1872-8332", "volume": "154", "pages": "161-175", "issn-l": null}, "abstract": "The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small-molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment. Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single-driver mutations have been implemented. Improvements in DNA- and RNA-based next-generation sequencing technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing. Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second- or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.", "doi": "10.1016/j.lungcan.2021.02.026", "pmid": "33690091", "labels": [], "xrefs": [{"db": "pii", "key": "S0169-5002(21)00086-6"}], "notes": [], "created": "2026-08-21T11:24:47.042Z", "modified": "2026-08-21T11:24:47.074Z"}], "created": "2026-08-20T08:00:23.523Z", "modified": "2026-08-20T08:00:23.523Z"}