{"entity": "researcher", "timestamp": "2026-08-20T20:51:24.608Z", "family": "V\u00e4lim\u00e4ki", "given": "Katja", "initials": "K", "orcid": "0000-0001-9117-7589", "affiliations": ["Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e4948127dec4455803fa8c74fefbde5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e4948127dec4455803fa8c74fefbde5"}}, "publications": [{"entity": "publication", "iuid": "cd554512c7194983b18c22de4faaeffd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cd554512c7194983b18c22de4faaeffd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cd554512c7194983b18c22de4faaeffd"}}, "title": "Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities.", "authors": [{"family": "Rantanen", "given": "Frida", "initials": "F", "orcid": "0009-0008-9597-5498", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b49cc1aef4fd4a2f9807429db8994086.json"}}, {"family": "Murum\u00e4gi", "given": "Astrid", "initials": "A"}, {"family": "Arjama", "given": "Mariliina", "initials": "M"}, {"family": "V\u00e4lim\u00e4ki", "given": "Katja", "initials": "K", "orcid": "0000-0001-9117-7589", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e4948127dec4455803fa8c74fefbde5.json"}}, {"family": "Multam\u00e4ki", "given": "Elina", "initials": "E"}, {"family": "Mirtti", "given": "Tuomas", "initials": "T"}, {"family": "Rannikko", "given": "Antti", "initials": "A"}, {"family": "Pellinen", "given": "Teijo", "initials": "T"}, {"family": "Ungureanu", "given": "Daniela", "initials": "D", "orcid": "0000-0002-9314-4972", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e3b69d0c4c647c0a0460d7ef0d66603.json"}}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}], "type": "journal article", "published": "2025-11-06", "journal": {"title": "Cell death discovery", "issn": "2058-7716", "volume": "11", "issue": "1", "pages": "507", "issn-l": "2058-7716"}, "abstract": "Cancer-associated fibroblasts (CAFs) are central architects of the prostate cancer (PCa) microenvironment, yet their phenotypic diversity and druggable vulnerabilities remain largely uncharted. Here, we present an integrative multi-omics characterization of primary ex vivo CAFs from seven treatment-na\u00efve PCa patients. Using single-cell RNA sequencing (scRNA-seq), we uncover substantial transcriptional heterogeneity among CAFs, with distinct gene expression programs related to extracellular matrix remodeling, inflammation, immune modulation, and metabolic reprogramming. This phenotypic diversity was further supported by variable expression of canonical stromal markers, including FAP, SULF1, VIM, CAV1, and \u03b1SMA. Transcription factor network analysis revealed SOX, FOX, and STAT3 family members as key regulators of pro-tumorigenic CAF states. To probe therapeutic vulnerabilities, we performed high-throughput drug sensitivity and resistance testing (DSRT) across 396 oncology compounds. CAFs exhibited broad sensitivity to multikinase inhibitors, with dasatinib, midostaurin, and FGFR inhibitors (AZD4547, erdafitinib) emerging as top stromal-directed candidates. These findings underscore the plasticity of prostate CAFs and reveal actionable vulnerabilities, supporting the development of targeted stromal therapies to disrupt tumor-stroma interactions in PCa.", "doi": "10.1038/s41420-025-02792-3", "pmid": "41198614", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12592484"}, {"db": "pii", "key": "10.1038/s41420-025-02792-3"}], "notes": [], "created": "2026-08-20T08:49:59.284Z", "modified": "2026-08-20T08:49:59.445Z"}, {"entity": "publication", "iuid": "a2d4d6d4a5c5405aa4e890d419216721", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a2d4d6d4a5c5405aa4e890d419216721.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a2d4d6d4a5c5405aa4e890d419216721"}}, "title": "Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.", "authors": [{"family": "Roos-Mattila", "given": "Matilda", "initials": "M", "orcid": "0000-0002-2834-3211", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9dd8feca623400d8e0c17b2725b6dc7.json"}}, {"family": "Kallio", "given": "Pauliina", "initials": "P", "orcid": "0000-0001-6374-6203", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/341466e88f824af587e257b73582d6dd.json"}}, {"family": "Luck", "given": "Tamara J", "initials": "TJ"}, {"family": "Polso", "given": "Minttu", "initials": "M"}, {"family": "Kumari", "given": "Romika", "initials": "R"}, {"family": "Mikkonen", "given": "Piia", "initials": "P"}, {"family": "V\u00e4lim\u00e4ki", "given": "Katja", "initials": "K", "orcid": "0000-0001-9117-7589", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e4948127dec4455803fa8c74fefbde5.json"}}, {"family": "Malmstedt", "given": "Minna", "initials": "M"}, {"family": "Ellonen", "given": "Pekka", "initials": "P"}, {"family": "Pellinen", "given": "Teijo", "initials": "T", "orcid": "0000-0001-9652-7373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e73595c0cc64a68a59cd95772784859.json"}}, {"family": "Heckman", "given": "Caroline A", "initials": "CA", "orcid": "0000-0002-4324-8706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a0490f5eb61a4d92a44815d03de84af4.json"}}, {"family": "Mustonen", "given": "Harri", "initials": "H", "orcid": "0000-0001-5632-6796", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f009308cd84542ae8c384fbfe87501d2.json"}}, {"family": "Puolakkainen", "given": "Pauli A", "initials": "PA"}, {"family": "Alitalo", "given": "Kari", "initials": "K", "orcid": "0000-0002-7331-0902", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d9a1a31264694e4fba6026b293655ff0.json"}}, {"family": "Kallioniemi", "given": "Olli", "initials": "O", "orcid": "0000-0002-3231-0332", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cb8605b07c884323afe4e1f2da37a031.json"}}, {"family": "Mirtti", "given": "Tuomas", "initials": "T", "orcid": "0000-0003-0455-9891", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c1963bc5086f4b45b9a48cb60115d578.json"}}, {"family": "Rannikko", "given": "Antti S", "initials": "AS"}, {"family": "Pieti\u00e4inen", "given": "Vilja M", "initials": "VM", "orcid": "0000-0003-3125-2406", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d24125e51334b94bce4ef70fed1e585.json"}}, {"family": "Sepp\u00e4nen", "given": "Hanna E", "initials": "HE"}], "type": "journal article", "published": "2024-10-20", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "7", "issue": "1", "pages": "1355", "issn-l": "2399-3642"}, "abstract": "Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.", "doi": "10.1038/s42003-024-07004-9", "pmid": "39427059", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11490566"}, {"db": "pii", "key": "10.1038/s42003-024-07004-9"}], "notes": [], "created": "2026-08-20T09:25:17.594Z", "modified": "2026-08-20T09:25:17.901Z"}]}