bortezomib

P4, N=450, Active, not recruiting, University of Turin, Italy | Recruiting --> Active, not recruiting

This model underscores the pivotal role of TME components in shaping therapeutic outcomes and offers a scalable, clinically translatable tool for personalized risk stratification. Our findings highlight the necessity of integrating microenvironmental insights into MM prognostication and pave the way for microenvironment-informed therapeutic decision-making.

P2, N=22, Recruiting, University of Utah | Trial primary completion date: Dec 2025 --> Dec 2026

HSP47 inhibition promotes immune evasion by upregulating CD155 via the TRAF2-NF-κB pathway, which impairs CD8+ T cell-mediated antitumor immunity. The combination of HSP47 inhibition with CD155/TIGIT blockade enhances therapeutic efficacy, suggesting a promising strategy for combination cancer therapies.

We constructed a RiskScore model for predicting the survival outcomes based on fibroblasts-related genes. These findings highlighted the role of fibroblasts in GBM development and offered six potential therapeutic targets (VWA1, DUSP6, LOXL1, IGFBP4, CYGB, and ZIC3) for GBM treatment. Additionally, immune infiltration analysis and drug sensitivity prediction further supported the model's utility in guiding personalized treatment of GBM.

Decreased NF-κB expression seems to be an independent prognostic factor for improved renal function. The results demonstrated for the first time the in vivo protein expression of MDM2 in the bone marrow of patients with multiple myeloma, as well as the possible effect of bortezomib on the expression of this protein in the microenvironment of multiple myeloma.

P2, N=160, Not yet recruiting, Massachusetts General Hospital

P3, N=614, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established. However, hypogammaglobulinemia was more common in the salvage group (75% vs. 15%, p = 0.018). This small case series suggests that DRd is promising for ASCT-eligible patients with MM after VCd failure.

Moreover, post-translational modifications (PTMs), including phosphorylation, acetylation, and oxidative stress, further modulate UPS activity and disease progression. Lastly, the review also evaluates emerging therapeutic strategies aimed at restoring proteostasis, including proteasome-targeting small molecules (e.g., bortezomib, IU1-47), natural compounds (e.g., curcumin, resveratrol), RNA-based therapies (e.g., miR-101, circHIPK3), and dietary approaches (e.g., Mediterranean and ketogenic diets), offering a foundation for future neurodegenerative disease treatment.

P2, N=50, Active, not recruiting, PETHEMA Foundation | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Dec 2025

CBX7 is a pivotal target for regulating cellular senescence in myeloma cells, operating through a novel CBX7/ERK/PIM1 regulatory axis. Targeting CBX7 and its downstream pathways may augment the efficacy of standard chemotherapy.