Evidence map›Paper›PMID 41198614›Full record

ArticleCell death discovery2025

Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities.

Frida Rantanen, Astrid Murumägi, Mariliina Arjama, Katja Välimäki, Elina Multamäki, Tuomas Mirtti, Antti Rannikko, Teijo Pellinen, Daniela Ungureanu, Olli Kallioniemi

Abstract read
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Frida Rantanen *Disease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0009-0008-9597-5498
Astrid Murumägi *Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Mariliina ArjamaInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Katja VälimäkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-9117-7589
Elina MultamäkiDisease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Tuomas MirttiResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Antti RannikkoResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Teijo PellinenInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Daniela UngureanuDisease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland. daniela.ungureanu@oulu.fi.ORCID http://orcid.org/0000-0002-9314-4972
Olli KallioniemiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. olli.kallioniemi@helsinki.fi.

Funding

Academy of Finland (Suomen Akatemia) 336449Academy of Finland (Suomen Akatemia) 360437
6 · The paper itself

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-naïve 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 αSMA. 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.

Identifiers

PMID41198614
PMCPMC12592484

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.