| Title: |
Abstract B076: TRIM24 degradation counteracts adaptation to androgen receptor inhibition in prostate cancer |
| Authors: |
Bossi, Daniela; Vallerga, Arianna; Salfi, Giuseppe; Formaggio, Nicolo; jichang, zhang; Bernasocchi, Tiziano; Rinaldi, Andrea; Bubendorf, Lukas; Mosole, Simone; Corey, Eva; Bolis, Marco; Pecoraro, Matteo; Geiger, Roger; Karthaus, Wouter R.; Mestre, Ricardo Pereira; Wang, Jinhua; Theurillat, Jean-Philippe Paul. |
| Publisher Information: |
American Association for Cancer Research (AACR) |
| Publication Year: |
2026 |
| Collection: |
Ecole Polytechnique Fédérale Lausanne (EPFL): Infoscience |
| Description: |
The androgen receptor (AR) is the primary therapeutic target in prostate cancer. While androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSi) are effective, the disease eventually progresses to fatal castration-resistant prostate cancer (CRPC). That said, little is known about the mechanisms in residual disease that initiates tumor relapse upon ADT/ARSi. Here, we discover a crucial role for TRIM24 in supporting the survival of residual cell clusters primed for tumor relapse in vivo. Consequently, reducing TRIM24 with bifunctional degraders (dTRIM24) significantly delays or even prevents the emergence of CRPC in the context of AR reactivation and lineage plasticity in vivo. dTRIM24 not only inhibits further AR signaling under ADT/ARSi but also counteracts adaptive pathways engaged by AR inhibition itself, such as STAT3 activation and EMT. Our findings underscore the potential of TRIM24 as an effective and druggable target for preventing prostate cancer progression under AR inhibition. Citation Format: Daniela Bossi, Arianna Vallerga, Giuseppe Salfi, Nicolo Formaggio, Zhang Jichang, Tiziano Bernasocchi, Andrea Rinaldi, Lukas Bubendorf, Simone Mosole, Eva Corey, Marco Bolis, Matteo Pecoraro, Roger Geiger, Wouter Karthaus, Ricardo Pereira Mestre, Jinhua Wang, Jean-Philippe Paul. Theurillat. TRIM24 degradation counteracts adaptation to androgen receptor inhibition in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B076. ; UPKARTHAUS |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0008-5472; 1538-7445 |
| Relation: |
Cancer Research; https://infoscience.epfl.ch/handle/20.500.14299/258442 |
| DOI: |
10.1158/1538-7445.prostateca26-b076 |
| Availability: |
https://doi.org/10.1158/1538-7445.prostateca26-b076; https://infoscience.epfl.ch/handle/20.500.14299/258442; https://hdl.handle.net/20.500.14299/258442 |
| Accession Number: |
edsbas.DD6D56BC |
| Database: |
BASE |