{"entity": "researcher", "timestamp": "2026-08-23T11:12:08.770Z", "family": "Maddalo", "given": "Gianluca", "initials": "G", "orcid": "0000-0003-2297-6488", "affiliations": ["Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbe53488c7848c582122063ecad8e2b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbe53488c7848c582122063ecad8e2b"}}, "publications": [{"entity": "publication", "iuid": "180db5f8ac7f49d291562d3050a7ba97", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/180db5f8ac7f49d291562d3050a7ba97.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/180db5f8ac7f49d291562d3050a7ba97"}}, "title": "Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy.", "authors": [{"family": "Karlsson", "given": "Max J", "initials": "MJ", "orcid": "0000-0002-7000-4416", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b93284f942e44f1086616357d77267c3.json"}}, {"family": "Costa Svedman", "given": "Fernanda", "initials": "F", "orcid": "0000-0001-8065-3375", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fdbe5b9759eb4ee0a13e66bd79cece06.json"}}, {"family": "Tebani", "given": "Abdellah", "initials": "A", "orcid": "0000-0002-8901-2678", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/794215a6625b4fe4b652ec08bcab98ec.json"}}, {"family": "Kotol", "given": "David", "initials": "D", "orcid": "0000-0002-5388-3826", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c41f8f491c474e6bba2047b5d04b4af5.json"}}, {"family": "H\u00f6iom", "given": "Veronica", "initials": "V"}, {"family": "Fagerberg", "given": "Linn", "initials": "L", "orcid": "0000-0003-0198-7137", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abbbf8193d5a4376a5c726768d039439.json"}}, {"family": "Edfors", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Egyhazi Brage", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-0524-2346", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b1b43df8e774c498fd4e1e16b00a5fc.json"}}, {"family": "Maddalo", "given": "Gianluca", "initials": "G", "orcid": "0000-0003-2297-6488", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbe53488c7848c582122063ecad8e2b.json"}}], "type": "journal article", "published": "2021-05-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "9", "pages": "2545-2555", "issn-l": "0008-5472"}, "abstract": "Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort. SIGNIFICANCE: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.", "doi": "10.1158/0008-5472.CAN-20-2000", "pmid": "33574091", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-2000"}], "notes": [], "created": "2026-08-21T12:28:54.568Z", "modified": "2026-08-21T12:28:54.740Z"}, {"entity": "publication", "iuid": "464e786d472b438891e36cd2ab1b17cb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/464e786d472b438891e36cd2ab1b17cb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/464e786d472b438891e36cd2ab1b17cb"}}, "title": "Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.", "authors": [{"family": "Das", "given": "Ishani", "initials": "I", "orcid": "0000-0002-2019-8072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c39c73355c644713825f2c45a3d8ddd4.json"}}, {"family": "Chen", "given": "Huiqin", "initials": "H"}, {"family": "Maddalo", "given": "Gianluca", "initials": "G", "orcid": "0000-0003-2297-6488", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbe53488c7848c582122063ecad8e2b.json"}}, {"family": "Tuominen", "given": "Rainer", "initials": "R"}, {"family": "Rebecca", "given": "Vito W", "initials": "VW"}, {"family": "Herlyn", "given": "Meenhard", "initials": "M", "orcid": "0000-0003-0839-0739", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccc202a013034554abe341033b9f6420.json"}}, {"family": "Hansson", "given": "Johan", "initials": "J"}, {"family": "Davies", "given": "Michael A", "initials": "MA", "orcid": "0000-0002-0977-0912", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9bcdfdf4b95f4df9af092b34a4d5e65b.json"}}, {"family": "Egyh\u00e1zi Brage", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-0524-2346", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b1b43df8e774c498fd4e1e16b00a5fc.json"}}], "type": "journal article", "published": "2020-10-20", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "11", "issue": "10", "pages": "882", "issn-l": "2041-4889"}, "abstract": "Current treatment modalities for disseminated cutaneous malignant melanoma (CMM) improve survival, however disease progression commonly ensues. In a previous study we identified afatinib and crizotinib in combination as a novel potential therapy for CMM independent of BRAF/NRAS mutation status. Herein, we elucidate the underlying mechanisms of the combination treatment effect to find biomarkers and novel targets for development of therapy that may provide clinical benefit by proteomic analysis of CMM cell lines and xenografts using mass spectrometry based analysis and reverse phase protein array. Identified candidates were validated using immunoblotting or immunofluorescence. Our analysis revealed that mTOR/Insulin signaling pathways were significantly decreased by the afatinib and crizotinib combination treatment. Both in vitro and in vivo analyses showed that the combination treatment downregulated pRPS6KB1 and pRPS6, downstream of mTOR signaling, and IRS-1 in the insulin signaling pathway, specifically ablating IRS-1 nuclear signal. Silencing of RPS6 and IRS-1 alone had a similar effect on cell death, which was further induced when IRS-1 and RPS6 were concomitantly silenced in the CMM cell lines. Silencing of IRS-1 and RPS6 resulted in reduced sensitivity towards combination treatment. Additionally, we found that IRS-1 and RPS6KB1 expression levels were increased in advanced stages of CMM clinical samples. We could demonstrate that induced resistance towards combination treatment was reversible by a drug holiday. CD171/L1CAM, mTOR and PI3K-p85 were induced in the combination resistant cells whereas AXL and EPHA2, previously identified mediators of resistance to MAPK inhibitor therapy in CMM were downregulated. We also found that CD171/L1CAM and mTOR were increased at progression in tumor biopsies from two matched cases of patients receiving targeted therapy with BRAFi. Overall, these findings provide insights into the molecular mechanisms behind the afatinib and crizotinib combination treatment effect and leverages a platform for discovering novel biomarkers and therapy regimes for CMM treatment.", "doi": "10.1038/s41419-020-03097-2", "pmid": "33082316", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7576205"}, {"db": "pii", "key": "10.1038/s41419-020-03097-2"}], "notes": [], "created": "2026-08-21T11:47:38.976Z", "modified": "2026-08-21T11:47:39.158Z"}]}