UTILISATION DES MODULATEURS DE L'ACTIVITE DU PROTEASOME DANS LE TRAITEMENT CONTRE LES CANCERS

Ndangang, Jeanne D'arc
(2026)

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Details

Supervisors
Vigneron, Nathalie
Faculty
Faculté de pharmacie et des sciences biomédicales
Degree label
Master [60] en sciences biomédicales
Abstract
enThe ubiquitin-proteasome system (UPS) plays a central role in tumour survival. Its dysregula-tion promotes the proliferation and adaptation of cancer celles, making the proteasome a major therapeutic target in haematological malignancies. This thesis is a critical literature review of six recent studies on multiple myeloma and acute lymphoblastic leukaemia(ALL). The analysis shows that selective targeting of the immunoproteasome is effective in KMT2A ::AFF1-rear-ranged ALL, that inhibition of the PSMD1 subunit by SiRNA bypasses resistance to classical inhibitors by activating the immunomodulatory cGAS-STING pathway, and that modulation of mithochondrial metabolism (OXPHOS) causally influences bortezomib sensitivity, with a cli-nically significant interaction observed with metformin. This work highligths the potential of proteasome- targeting strategies in a precision medecine perspective and paves the way for multimodal approaches integrating predictive biomarkers and immunotherapy. Keywords : proteasome; proteasome inhibitors; immunoproteasome; multiple myeloma; acute lymphoblastic leukaemia; PSMD1; mitochondrial metabolism.