Resistance to Proteasome Inhibitor Therapy in Non-Hodgkin Lymphoma

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


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.


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



Activated B-Cell


Acute Lymphoblastic Leukemia


Acute Myeloid Leukemia


Cyclophosphamide, Doxorubicin, Vincristine, Prednisone


Children’s Oncology Group


Central Nervous System


Complete Response


Diffuse Large B-Cell Lymphoma


Deubiquitinating Enzymes


Ubiquitin-Activating Enzyme


Ubiquitin-Conjugating Enzyme


Ubiquitin-Protein Ligases


Endoplasmic Reticulum


Food and Drug Administration


Germinal Center B-Cell Type


Hodgkin Lymphoma


Half Maximum Inhibitory Concentration




Lymphoblastic Lymphoma


Mantle Cell Lymphoma


Major Histocompatibility Complex


Multiple Myeloma


Non-Hodgkin Lymphoma


Overall Survival


Overall Response Rate


Progression-Free Survival


Primary Mediastinal large B-Cell Lymphoma


Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone




Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone


Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed.


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Copyright information

© 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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