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Targeting Translation of mRNA as a Therapeutic Strategy in Cancer

  • B-cell NHL, T-cell NHL, and Hodgkin Lymphoma (J Amengual, Section Editor)
  • Published:
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Abstract

Purpose of Review

To highlight recent results in targeting mRNA translation and discuss the results and prospects of translation inhibitors in cancer therapy.

Recent Findings

Until recently, inhibitors of mRNA translation have been thought to likely lack a therapeutic window. In 2012, the Food and Drug Administration (FDA) approved omacetaxine mepesuccinate (homoharringtonine) for the treatment of adults with chronic myelogenous leukemia (CML) who are resistant to at least two tyrosine kinase inhibitors. Since then, a few drugs, notably tomivosertib (eFT-508), selinexor (KPT-330), and ribavirin, have entered clinical trials. These drugs are known to inhibit mRNA translation. More recently, a number of interesting studies report that discrete subsets of proteins in cancer cells may be selectively targeted at the translation step, through inhibiting signals such as phospho-4E-BP1, eIF4A, and eIF4E. Promising therapies using these strategies have demonstrated potent anti-tumor activity in preclinical cancer models.

Summary

The growing number of translation inhibitors with diverse mechanisms, coupled with emerging insights into translational regulation of different cancer-promoting genes, suggests a bright new horizon for the field of therapeutic targeting of mRNA translation in cancer.

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  1. Department of Medicine, Center for Lymphoid Malignancies, Columbia University Irving Medical Center, New York, NY, USA

    Ipsita Pal & Changchun Deng

  2. Divison of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Maryam Safari & Susan E. Bates

  3. Department of Biological Sciences, Columbia University, New York, NY, USA

    Marko Jovanovic

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  1. Ipsita Pal
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  2. Maryam Safari
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  3. Marko Jovanovic
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  4. Susan E. Bates
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  5. Changchun Deng
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Correspondence to Changchun Deng.

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Conflict of Interest

Ipsita Pal, Maryam Safari, Marko Jovanovic, and Susan E. Bates declare that they have no conflict of interest.

Changchun Deng reports grants from TG Therapeutics and Amgen. In addition, Dr. Deng has two patents pending related to the topic reviewed here: 15003-353US0 and IR# CU19337.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on B-cell NHL, T-cell NHL, and Hodgkin Lymphoma

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Pal, I., Safari, M., Jovanovic, M. et al. Targeting Translation of mRNA as a Therapeutic Strategy in Cancer. Curr Hematol Malig Rep 14, 219–227 (2019). https://doi.org/10.1007/s11899-019-00530-y

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