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Resistance to Proteasome Inhibitor Therapy in Non-Hodgkin Lymphoma

  • Rodney R. Miles
  • Paul J. GalardyEmail author
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 21)

Abstract

The proteasome is a cytosolic proteolytic system that not only degrades damaged proteins but also has a critical role in cellular function through highly-regulated, targeted degradation of proteins. Inhibition of the proteasome system has been shown to have therapeutic potential in certain hematological malignancies. In this chapter, we will provide an overview of the ubiquitin proteasome system, focusing our discussion in the mechanisms of action and resistance to small molecule proteasome inhibitors currently approved or in development for therapeutic use in cancer.

Keywords

Proteasome inhibitors Non-Hodgkin lymphoma Ubiquitin-activating enzymes Ubiquitin-conjugating enzymes Bortezomib 

Abbreviations

ABC

Activated B-Cell

ALL

Acute Lymphoblastic Leukemia

AML

Acute Myeloid Leukemia

CHOP

Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

COG

Children’s Oncology Group

CNS

Central Nervous System

CR

Complete Response

DLBCL

Diffuse Large B-Cell Lymphoma

DUB

Deubiquitinating Enzymes

E1

Ubiquitin-Activating Enzyme

E2

Ubiquitin-Conjugating Enzyme

E3

Ubiquitin-Protein Ligases

ER

Endoplasmic Reticulum

FDA

Food and Drug Administration

GCB

Germinal Center B-Cell Type

HL

Hodgkin Lymphoma

IC50

Half Maximum Inhibitory Concentration

IHC

Immunohistochemical

LL

Lymphoblastic Lymphoma

MCL

Mantle Cell Lymphoma

MHC

Major Histocompatibility Complex

MM

Multiple Myeloma

NHL

Non-Hodgkin Lymphoma

OS

Overall Survival

ORR

Overall Response Rate

PFS

Progression-Free Survival

PMBCL

Primary Mediastinal large B-Cell Lymphoma

R-CHOP

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

R/R

Relapsed/Refractory

VR-CAP

Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone

Notes

Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PathologyUniversity at UtahSalt Lake CityUSA
  2. 2.ARUP Institute for Clinical & Experimental PathologySalt Lake CityUSA
  3. 3.Department of Pediatric and Adolescent MedicineMayo ClinicRochesterUSA
  4. 4.Department of Biochemistry and Molecular BiologyMayo ClinicRochesterUSA
  5. 5.Division of Pediatric Hematology-OncologyMayo ClinicRochesterUSA

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