Furthermore, we identified several potential therapeutic agents, including imatinib and bortezomib. Collectively, our dual-model framework provides a tool for risk stratification, offers translational insights for precision treatment, and presents new directions for understanding TNBC heterogeneity and therapeutic development.

Background/Objectives: Carfilzomib (CFZ) and bortezomib (BTZ) are proteasome inhibitors used as the first-line therapy for relapsed or refractory multiple myeloma (MM) but are associated with cardiovascular adverse events (CVAEs). Pathway enrichment analyses identified peroxisome, MAPK, Rap1, adherens junction, phospholipase D, autophagy, and aldosterone-related pathways to be implicated in CVAEs. Our study identified distinct DMPs, DMRs, and pathways enrichment associated with CVAE, suggesting epigenetic contributors to CVAEs and supporting the need for larger validation studies.

A panel of human and murine breast cancer cell lines was treated with the IDH2 inhibitor AGI-6780, alone or in combination with the proteasome inhibitor carfilzomib (CFZ) or the E1 ubiquitin-activating enzyme inhibitor TAK-243. Inhibition of IDH2 markedly enhances the cytotoxic effects of proteasome-targeting by disrupting metabolic-proteostatic balance and promoting apoptotic cell death. These findings identify a growth-inhibitory effect that may be leveraged to improve functional dependency in breast cancer, particularly in triple-negative breast cancer, which currently lacks efficient drug treatments.

DK-7, a quinoxaline-based UCHL5 inhibitor, selectively triggers ER stress and apoptosis, effectively overcomes bortezomib resistance, and exhibits antitumor activity in solid tumors. These findings highlight UCHL5 as a promising therapeutic target and suggest quinoxaline-based DUB inhibitors as a next-generation proteasome-targeted strategy with broad clinical potential.

Moreover, of the genes analyzed, the expression of NFκB1 was significantly downregulated in 2D cultures in all tested cells treated with BOR alone or in combination with DOX. Overall, the study sheds light on the differences in drug responses and gene expression profiles between 2D and 3D culture models under single and combination treatments, emphasizing the increased physiological importance of 3D systems in simulating in vivo tumor behavior.

She underwent leukapheresis, hydroxyurea for cytoreduction, and bortezomib-dexamethasone for myeloma. In elderly patients with cytopenias and monocytosis, thorough diagnostic workup is crucial. This case emphasizes the need for personalized therapy in complex hematologic overlap syndromes.

P=N/A, N=200, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

P2, N=25, Completed, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Completed | N=55 --> 25

Furthermore, Bortezomib suppressed CHI3L1 secretion in vitro and in vivo, inhibiting HCC lung metastasis. This study establishes CHI3L1 as a specific biomarker and a therapeutic target for HCC pulmonary metastasis.

Consider gamma heavy-chain disease in patients with unexplained monoclonal gammopathy and atypical presentations, such as hypercalcaemia and ascites.A combination of rituximab and chemotherapy shows an anti-tumour effect in gamma heavy-chain disease expressing CD20.

Cycloheximide chase assays, PS-341, and chloroquine treatment were used to explore the mechanisms of PD-1 downregulatory effects by apigenin...In vivo experiments confirmed that combined treatment noticeably inhibited melanoma growth and enhanced T cell infiltration into melanoma tissues. Apigenin promoted the degradation of PD-1 in T cells via the proteasomal pathway, in addition to synergizing with chemo/radiotherapy to inhibit melanoma growth.

P2, N=130, Recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2027 --> Sep 2030