Evidence map›Paper›PMID 40949972›Full record

ArticlebioRxiv : the preprint server for biology2025

A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules.

Phillip Thienger, Irene Paassen, Xiaosai Yao, Philip D Rubin, Marika Lehner, Nicholas Lillis, Andrej Benjak, Sagar R Shah, Alden King-Yung Leung, Simone de Brot and 16 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Phillip ThiengerDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Irene PaassenDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.ORCID 0009-0000-7737-3292
Xiaosai YaoDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Philip D RubinDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Marika LehnerDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Nicholas LillisDepartment of Urology, University of California, San Francisco, CA, USA.
Andrej BenjakDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.ORCID 0000-0003-4522-6575
Sagar R ShahDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Alden King-Yung LeungDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Simone de BrotCOMPATH, Institute of Animal Pathology, University of Bern, Bern, Switzerland.ORCID 0000-0003-3049-0103
Alina NaveedDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Bence DanielDepartment of Proteomics and Genomic Technologies, Genentech, South San Francisco, CA 94080.
Minyi ShiDepartment of Proteomics and Genomic Technologies, Genentech, South San Francisco, CA 94080.
Julien TremblayDepartment of Computational Sciences, Genentech, South San Francisco, CA, USA.
Joanna TriscottDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Giada Andrea CassanmagnagoComputational Oncology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, Via Mario Negri 2, 20156 Milano, Italy.
Marco BolisComputational Oncology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, Via Mario Negri 2, 20156 Milano, Italy.
Lia MelaDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.
Himisha BeltranDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yu ChenHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Salvatore PiscuoglioIRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy.ORCID 0000-0003-2686-2939
Haiyuan YuDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Charlotte K Y NgSIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.ORCID 0000-0002-6100-0026
David A QuigleyDepartment of Urology, University of California, San Francisco, CA, USA.
Robert L YauchDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.ORCID 0000-0001-9478-6283
Mark A RubinDepartment for Biomedical Research, University of Bern, Bern, 3008, Switzerland.

Funding

UCSF Specialized Programs of Research Excellence (SPOREs) in Prostate CancerP50CA275741 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PETER R CARROLL · 2024 to 2026
$8.8M
NCI NIH HHS P50 CA275741
6 · The paper itself

Abstract

Proteolysis targeting chimera (PROTAC) therapies degrading SWI/SNF ATPases offer a novel approach to interfere with androgen receptor (AR) signaling in AR-dependent castration-resistant prostate cancer (CRPC-AR). To explore the utility of SWI/SNF therapy beyond AR-sensitive CRPC, we investigated SWI/SNF-targeting agents in AR-negative CRPC. SWI/SNF targeting PROTAC treatment of cell lines and organoid models reduced the viability of not only CRPC-AR but also WNT-signaling dependent AR-negative CRPC (CRPC-WNT). The CRPC-WNT subgroup represents 11% of around 400,000 cases of CRPC worldwide who die yearly of CRPC. We discovered that SWI/SNF ATPase SMARCA4 depletion interfered with the master transcriptional regulator TCF7L2 (TCF4) in CRPC-WNT. Functionally, TCF7L2 maintains proliferation via the MAPK signaling axis in this subtype of CRPC. These data suggest a mechanistic rationale for interventions that perturb the DNA binding of the pro-proliferative TCF7L2 transcription factor (TF) and/or direct MAPK signaling inhibition in the CRPC-WNT subclass of advanced prostate cancer.

Identifiers

PMID40949972
PMCPMC12424701

What OpenQuestion holds

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Registered trials

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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.