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Resistance to Histone Deacetylase Inhibitors in the Treatment of 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

Outcomes for patients with lymphoma have improved through the use of chemo/immunotherapy. However, therapy for patients with advanced disease and relapsed/refractory disease remains inadequate. In addition, off target side effects result in significant short and long-term toxicity. The use of targeted molecular therapy introduces an opportunity for improvement in efficacy and reduction in undesirable off target effects. Histone Deacetylase (HDAC) inhibitors are a class of targeted molecular therapies that have been extensively evaluated for the treatment of refractory malignancies including subtypes of lymphoma. However, critical resistance mechanisms are well described. Optimal efficacy of HDAC inhibitors in the treatment of lymphoma is dependent upon successful strategies to overcome drug resistance.

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Abbreviations

AITL:

Angioimmunoblastic T-Cell Lymphoma

AML:

Acute Myeloid Leukemia

CHOP:

Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

CR:

Complete Response

CTCL:

Cutaneous T-Cell Lymphoma

DLBCL:

Diffuse Large B-Cell Lymphoma

ER:

Endoplasmic Reticulum

FDA:

Food and Drug Administration

FL:

Follicular Lymphoma

HAT:

Histone acetyltransferase

HDAC:

Histone Deacetylase

HDACi:

HDAC inhibitors

HL:

Hodgkin Lymphoma

MCL:

Mantle Cell Lymphoma

MM:

Multiple Myeloma

MZL:

Marginal Zone Lymphoma

NAD:

Nicotinamide Adenine Dinucleotide

NHL:

Non-Hodgkin Lymphoma

OR:

Overall Response

ORR:

Overall Response Rate

PCTCL:

Primary Cutaneous T-Cell Lymphoma

PFS:

Progression-Free Survival

PR:

Partial Response

PTCL:

Peripheral T-Cell Lymphoma

r/r:

relapsed/refractory

SLL:

Small Lymphocytic Lymphoma

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Acknowledgements

AF reviewed the literatures, developed the design of the paper and wrote the manuscript. OA critically revised the manuscript and have approved the final version for publication. The authors would like to thank Erin Morris, RN for her excellent assistance with the preparation of this manuscript.

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No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, New York Medical College, Valhalla, NY, USA

    Allyson Flower

  2. The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Oussama Abla

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  1. Allyson Flower
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  2. Oussama Abla
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Correspondence to Allyson Flower .

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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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Flower, A., Abla, O. (2019). Resistance to Histone Deacetylase Inhibitors in the Treatment of 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_5

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