Purpose of Review
To highlight recent results in targeting mRNA translation and discuss the results and prospects of translation inhibitors in cancer therapy.
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.
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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Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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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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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
- Translation inhibitor