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A metabolic switch in proteasome inhibitor-resistant multiple myeloma ensures higher mitochondrial metabolism, protein folding and sphingomyelin synthesis
- Publication Year :
- 2019
- Publisher :
- Ferrata Storti Foundation, 2019.
-
Abstract
- Proteasome inhibitors (PI) have evolved as the central backbone of treatment for multiple myeloma (MM), with first-in-class bortezomib and second- and third-generation PI, carfilzomib and ixazomib, having been approved for this indication. Proteasome inhibition disrupts the unfolded protein response to resolve excessive endoplasmic reticulum stress, but also leads to massive metabolic changes manifested by the induction of amino acid biosynthesis, an anti-oxidant response, lipogenesis and an increase in protein folding. In this sense, PI represent a unique class of drugs targeting cancer cell metabolism by affecting the balance between protein biosynthesis, folding and destruction. However, the adaptive changes in MM cell metabolism may provide the basis of resistance to PI, as high glycolytic activity or rewiring glucose metabolism is associated with bortezomib resistance in MM.
- Subjects :
- Proteasome Endopeptidase Complex
Protein Folding
Antineoplastic Agents
Ixazomib
Bortezomib
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
medicine
Protein biosynthesis
Homeostasis
Humans
Metabolomics
Online Only Articles
030304 developmental biology
Aged
0303 health sciences
Endoplasmic reticulum
Gene Expression Profiling
Hematology
Hydrogen Peroxide
Middle Aged
Carfilzomib
Lipids
3. Good health
Cell biology
Mitochondria
Sphingomyelins
Gene Expression Regulation, Neoplastic
Proteasome
chemistry
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Proteasome inhibitor
Unfolded protein response
Female
Multiple Myeloma
Reactive Oxygen Species
Oligopeptides
Proteasome Inhibitors
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....18563cd9d2a40b7b9959a249fde33ec3