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.

Treatment with the KXD regimen (carfilzomib, cyclophosphamide, dexamethasone) resulted in transient disease stabilization for approximately two months, followed by further progression. In addition, infiltration of CD138-positive plasma cell-like tumor cells with λ light chain restriction was observed in the gastric lamina propria, consistent with extramedullary disease (EMD). The final diagnosis was relapsed MM complicated by sPCL, gastric mucosal extramedullary plasmacytic infiltration, and synchronous moderately differentiated intramucosal papillary adenocarcinoma.

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.

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.

In vivo experiments confirmed that WYC-209 potentiated the antitumor efficacy of CFZ by upregulating ZMYND8, thereby ameliorating tumor burden in NSG mice. These findings establish that targeting ZMYND8 with the novel retinoid WYC-209 potently enhances the efficacy of CFZ and holds translational promise for improving clinical outcomes in patients with MM.

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.

Post-ASCT2 maintenance, particularly with lenalidomide or carfilzomib-based regimens, significantly prolonged disease control in randomized and real-world studies. In the modern treatment landscape, second or salvage autologous transplantation remains a valid, safe, and effective strategy for carefully selected patients with relapsed multiple myeloma, particularly those with chemosensitive disease and prolonged initial remissions. ASCT2 should be integrated in a risk-adapted manner alongside maintenance therapy and emerging immunotherapies, serving as a durable consolidation or bridging approach rather than routine therapy for all relapsed patients.

High plasma cell-like phenotype signatures were linked to poorer progression-free survival (PFS) but greater benefit from R-CHOP plus bortezomib, while low-signature patients achieved better PFS with R-CHOP alone. These findings characterize the transcriptomic features of distinct plasma cell-like phenotypes in DLBCL, providing new insights into its prognostic relevance and potential for individualized treatment strategies.