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Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care.
View Article and Find Full Text PDFLongitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFCombination effects of Pistachio hull and carfilzomib on NF-κB p65, MDR1, MRP1, and Caspase3 gene expression in breast cancer cell line.
BMC Complement Med Ther
January 2025
Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Objective: This study aimed to investigate the synergistic effects of the chemotherapy drug Carfilzomib (CFZ) and Pistachio hull extract on the SK-BR3 breast cancer cell line.
Methods: In this experimental study, we evaluated the effect of Pistachio hull extract and CFZ as standalone treatments on cell viability using the MTT assay at 24- and 48-hours post-treatment. Following this, we conducted combination therapy analyses to assess the potential synergistic relationship between Pistachio hull extract and CFZ after 24- and 48-hours of treatment on both the SK-BR3 breast cancer cell line and the MCF10A normal cell line.
In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD.
View Article and Find Full Text PDFProteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects.
J Hematol Oncol
January 2025
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Background: Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated.
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