bortezomib

P1, N=18, Not yet recruiting, M.D. Anderson Cancer Center

Synergistic effects with bortezomib (BTZ) were analyzed...SNG exerts potent anticancer effects in CTCL by inducing ROS-dependent mitochondrial apoptosis and inhibiting the PI3K/AKT/GSK3 signaling pathway. Its synergy with BTZ and computational validation of AKT/Bcl-2 targeting underscore its potential as a novel therapeutic candidate for CTCL, warranting further preclinical investigation.

Notably, PS elevated intracellular reactive oxygen species (ROS), and scavenging ROS with N-acetylcysteine (NAC) significantly attenuated PS-driven cytotoxicity, supporting a ROS-dependent mechanism. Finally, PS combined with the proteasome inhibitor bortezomib produced greater anti-CTCL activity than either agent alone, consistent with a synergistic interaction. Together, these findings show that PS promotes ROS-dependent, mitochondria-mediated apoptosis in CTCL and support further evaluation of PS-based strategies for this malignancy.

Although Dara-VTd induction is associated with impaired mobilization kinetics, successful steady-state mobilization remains feasible. On-demand plerixafor use overcomes mobilization deficits, supporting this approach in patients receiving CD38-based quadruplet induction therapy. Furthermore, follow-up analysis of stem cell graft utilization demonstrates a high proportion of collected but unused stem cell grafts in both cohorts.

P3, N=939, Active, not recruiting, Celgene | Trial primary completion date: Mar 2026 --> Nov 2027

Finally, autophagy-related analyses demonstrated increased LC3B-II levels accompanied by p62 accumulation, suggesting altered autophagic processing rather than simple activation of autophagy. Collectively, these findings demonstrate that bortezomib exerts cytotoxic effects in Ut-LMS cells through coordinated regulation of proteasome inhibition-associated apoptosis, cell cycle control, mitochondrial dysfunction, and autophagy-related signaling, with cell line-specific differences in stress response pathways.

Therapeutic strategies including activation of NK cells via chemotherapeutics (bortezomib, decitabine), blockade of inhibitory receptors (NKG2A, CD161), and combinatorial approaches with immune checkpoint inhibitors are under active investigation. Notably, chimeric antigen receptor (CAR)-engineered NK cells targeting EGFR, HER2, GD2, and CD133 show promise in preclinical glioma models due to their enhanced specificity and reduced toxicity compared to CAR-T cells. This review summarizes the multifaceted roles of NK cells in glioma immunity and highlights novel immunotherapeutic strategies to restore NK cell function and improve clinical outcomes.

These findings suggest that while MPO inhibition may not enhance efficacy of bortezomib induction therapy, it holds promise as a maintenance strategy to improve long-term outcomes in MM. Collectively, our data support further investigation of AZD5904 as a novel maintenance therapy targeting the BM microenvironment, with potential to enhance and sustain the effectiveness of existing, standard of care regimens.

Our findings highlight ABCB1 promoter hypomethylation as a potential epigenetic driver of CFZ resistance in MM. These results underscore the clinical relevance of epigenetic regulation in drug resistance and the potential of targeting DNA methylation as a therapeutic strategy to overcome resistance in MM.

In addition, GAS significantly inhibited aberrant NF-κB signaling and upregulation of NLRP3 inflammasome-related proteins of BIPN mice. GAS may alleviate BIPN by suppressing microglia-mediated neuroinflammatory responses, and the NF-κB/NLRP3 inflammasome signaling pathway appears to be involved in this process.

Two patients who had relapsed after CAR T-cell treatment with idecabtagene vicleucel achieved partial and very good partial responses and were successfully transitioned to a second CAR T-cell therapy with ciltacabtagene autoleucel. SVd demonstrates meaningful activity in patients with penta-refractory MM and prior failure of BCMA/GPRC5D-targeted immunotherapies. The ORR of 61%, disease control in 78% of patients, and median PFS of 4.3 months support further evaluation of SVd in this highly refractory setting after failure of BCMA- and GPRC5D-directed approaches.

Notably, 7n displayed the strongest inhibitory activities against JAK3 in 76 kinase profiles with the inhibitory rate of 96.87% at the concentration of 5 nM. Altogether, these findings suggest that JAK3 is a potential target to develop the inhibitor for treating Bortezomib-resistant multiple myeloma and 7n can be considered a promising candidate for further research.