RAS gene mutations occur in 30 - 40% of multiple myeloma (MM) patients. Farnesylation is the first step in the post-translational modification of RAS proteins. Tipifarnib is a potent farnesyl transferase inhibitor, and incadronate prevents post-translational prenylation of GTP-binding proteins such as RAS proteins. We examined the effect of tipifarnib in combination with incadronate on the growth of fresh and cloned myeloma cells in vitro. Tipifarnib inhibited the growth of myeloma cells, and this inhibition was intensified when tipifarnib was combined with incadronate. Tipifarnib, in combination with incadronate, may have some benefits in MM patients.
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http://dx.doi.org/10.1080/10428190500221223 | DOI Listing |
J Immunother Cancer
January 2025
Rapa Therapeutics, Rockville, Maryland, USA.
Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.
View Article and Find Full Text PDFPLoS One
January 2025
Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.
View Article and Find Full Text PDFHematology
December 2025
Department of Hematology, XuChang Central Hospital, XuChang, People's Republic of China.
Introduction: Mitochondria and angiogenesis play key roles in multiple myeloma (MM) development, but their interrelated genes affecting MM prognosis are under-studied.
Methods: We analyzed TCGA_MMRF and GSE4581 datasets to identify four genes - CCNB1, CDC25C, HSP90AA1, and PARP1 - that significantly correlate with MM prognosis, with high expression indicating poor outcomes.
Results: A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the latter showing better survival.
Background: Anti-CD38 monoclonal antibodies (mAbs) have significantly changed the multiple myeloma treatment landscape. This meta-analysis compared the efficacy and safety of anti-CD38 mAb-based therapy versus standard therapy in newly diagnosed multiple myeloma (NDMM) patients.
Methods: We performed a comprehensive literature search on PubMed, the Cochrane Database, and ClinicalTrials.
Cancer Metab
January 2025
Department of Cardiovascular medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
The Warburg effect, characterized by the shift toward aerobic glycolysis, is closely associated with the onset and advancement of tumors, including multiple myeloma (MM). Nevertheless, the specific regulatory mechanisms of glycolysis in MM and its functional role remain unclear. In this study, we identified that growth differentiation factor 15 (GDF15) is a glycolytic regulator, and GDF15 is highly expressed in MM cells and patient samples.
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