(+34) 93 414 55 66
Contact
Espacio socios y amigos
The Translational Research Group in Lymphoma at the Josep Carreras Leukaemia Research Institute has discovered that reducing TRIM24 levels in mantle cell lymphoma could help overcome resistance to standard chemotherapy with bortezomib and restore drug sensitivity during treatment. This study, the result of an international collaboration, employed innovative approaches to lay the groundwork for future research in human patients following preliminary testing in preclinical models.
Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin lymphoma characterized by a high relapse rate in patients. Bortezomib, one of the most commonly used chemotherapies, is a drug that inhibits the proteasome—an essential system responsible for the removal of unnecessary proteins within the cell and for maintaining cellular function.
Treatment resistance is a concerning issue for patients, as it narrows their therapeutic options. To better understand how this resistance develops, a research team led by Dr. Núria Profitós (Josep Carreras Institute), Corentin Bouvier, and María González-Santamarta (both from the Coordination Chemistry Laboratory–CNRS, Toulouse), studied the involved cellular systems and identified a key player: TRIM24.
According to the study, recently published in the prestigious Cell Death Discovery journal from the Nature group, MCL cells resistant to bortezomib show elevated levels of TRIM24 compared to cells that remain sensitive to the drug. This increase may induce a switch between two different protein degradation systems: the proteasome and autophagy. Once bortezomib inhibits the former, the switch to the latter allows the cancer cells to survive treatment. This raised a key question: What would happen if TRIM24 levels were reduced?
Thanks to in ovo preclinical models—a more advanced methodology that studies human cancer development in more complex animal models—the team confirmed that reducing TRIM24 in MCL cells successfully restores sensitivity to bortezomib. In fact, when tumors were treated with a combination of bortezomib and a PROTAC targeting TRIM24 (a selective drug that degrades TRIM24 inside the cell), previously resistant cancer cells died at a significantly higher rate.
The next step will be to bring these findings into the clinical setting to determine whether the preclinical results can be replicated in human patients. Furthermore, this study has demonstrated that emerging technologies, such as in ovo preclinical models and PROTAC drugs—whether used alone or in combination—could become powerful anticancer strategies for lymphomas and other types of cancer in the coming years.
This research was partially funded by the EU Horizon 2020 program (UbiCODE project), the French Téléthon, the Fondation Toulouse Cancer Santé (PROTRIM project), the REPERE and prématuration (ubipièges) programs of Occitania, the Spanish Health Research Fund, and the European Regional Development Fund (FEDER) through the Interreg V-A Spain-France-Andorra (POCTEFA) program (PROTEOblood). No generative artificial intelligence tools were used in the preparation of this news.
Reference article:
Bouvier, C., Gonzalez-Santamarta, M., Profitós-Pelejà, N. et al. Role of TRIM24 in the regulation of proteasome-autophagy crosstalk in bortezomib-resistant mantle cell lymphoma. Cell Death Discov. 11, 108 (2025). https://doi.org/10.1038/s41420-025-02355-nm.
