J 2019

A metabolic switch in proteasome inhibitor-resistant multiple myeloma ensures higher mitochondrial metabolism, protein folding and sphingomyelin synthesis

BESSE, Lenka, Andrej BESSE, Max MENDEZ-LOPEZ, Kateřina VAŠÍČKOVÁ, Miroslava SEDLÁČKOVÁ et. al.

Basic information

Original name

A metabolic switch in proteasome inhibitor-resistant multiple myeloma ensures higher mitochondrial metabolism, protein folding and sphingomyelin synthesis

Authors

BESSE, Lenka (756 Switzerland, guarantor), Andrej BESSE (756 Switzerland), Max MENDEZ-LOPEZ (756 Switzerland), Kateřina VAŠÍČKOVÁ (203 Czech Republic, belonging to the institution), Miroslava SEDLÁČKOVÁ (203 Czech Republic, belonging to the institution), Petr VAŇHARA (203 Czech Republic, belonging to the institution), Marianne KRAUS (756 Switzerland), Jurgen BADER (756 Switzerland), Renan B. FERREIRA (840 United States of America), Ronald K. CASTELLANO (840 United States of America), Brian K. LAW (840 United States of America) and Christoph DRIESSEN (756 Switzerland)

Edition

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2019, 0390-6078

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 7.116

RIV identification code

RIV/00216224:14110/19:00110883

Organization unit

Faculty of Medicine

DOI

UT WoS

000483996100008

Keywords in English

metabolic switch; proteasome inhibitor; multiple myeloma

Tags

Tags

International impact, Reviewed
Změněno: 7/10/2019 09:30, Mgr. Tereza Miškechová

Abstract

V originále

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.