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Resistance to Proteasome Inhibitor Therapy in Non-Hodgkin Lymphoma

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Resistance to Targeted Therapies in Lymphomas

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((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.

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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

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Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed.

Author information

Authors and Affiliations

  1. Department of Pathology, University at Utah, Salt Lake City, UT, USA

    Rodney R. Miles

  2. ARUP Institute for Clinical & Experimental Pathology, Salt Lake City, UT, USA

    Rodney R. Miles

  3. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA

    Paul J. Galardy

  4. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA

    Paul J. Galardy

  5. Division of Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN, USA

    Paul J. Galardy

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  1. Rodney R. Miles
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Corresponding author

Correspondence to Paul J. Galardy .

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Editors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, University of Alabama at Birmingham Children’s Hospital of Alabama, Birmingham, AL, USA

    Ana C. Xavier

  2. Departments of Pediatrics, Medicine, Pathology, Microbiology and Immunology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    Mitchell S. Cairo

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Miles, R.R., Galardy, P.J. (2019). Resistance to Proteasome Inhibitor Therapy in Non-Hodgkin Lymphoma. In: Xavier, A., Cairo, M. (eds) Resistance to Targeted Therapies in Lymphomas . Resistance to Targeted Anti-Cancer Therapeutics, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-030-24424-8_4

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