Next Article in Journal
An Improved Weighted Partial Least Squares Method Coupled with Near Infrared Spectroscopy for Rapid Determination of Multiple Components and Anti-Oxidant Activity of Pu-Erh Tea
Next Article in Special Issue
Design, Synthesis, and In Vitro Evaluation of Novel Histone H3 Peptide-Based LSD1 Inactivators Incorporating α,α-Disubstituted Amino Acids with γ-Turn-Inducing Structures
Previous Article in Journal
Analysis of Menaquinone-7 Content and Impurities in Oil and Non-Oil Dietary Supplements
Previous Article in Special Issue
Targeting GLI Transcription Factors in Cancer
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessFeature PaperReview
Molecules 2018, 23(5), 1057; https://doi.org/10.3390/molecules23051057

Targeting General Transcriptional Machinery as a Therapeutic Strategy for Adult T-Cell Leukemia

1
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
2
Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka 020-8505, Iwate, Japan
3
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
4
14 Medical Drive, Centre for Translational Medicine, #12-01, Singapore 117599, Singapore
*
Author to whom correspondence should be addressed.
Received: 17 March 2018 / Revised: 27 April 2018 / Accepted: 28 April 2018 / Published: 2 May 2018
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)
Full-Text   |   PDF [1496 KB, uploaded 2 May 2018]   |  

Abstract

Cancer cells are highly reliant on certain molecular pathways, which support their survival and proliferation. The fundamental concept of molecularly targeted therapy is to target a protein that is specifically deregulated or overexpressed in cancer cells. However, drug resistance and tumor heterogeneity are major obstacles in the development of specific inhibitors. Additionally, many driver oncogenes exert their oncogenic property via abnormal expression without having genetic mutations. Interestingly, recent accumulating evidence has demonstrated that many critical cancer genes are driven by a unique class of enhancers termed super-enhancers. Genes associated with super-enhancers are relatively more susceptible to the inhibition of general transcriptional machinery compared with genes that are regulated by typical enhancers. Cancer cells are more sensitive to treatment with small-molecule inhibitors of CDK7 or BRD4 than non-transformed cells. These findings proposed a novel strategy to identify functionally important genes as well as novel therapeutic modalities in cancer. This approach would be particularly useful for genetically complicated cancers, such as adult T-cell leukemia (ATL), whereby a large mutational burden is present, but the functional consequences of each mutation have not been well-studied. In this review, we discuss recent findings on super-enhancers, underlying mechanisms, and the efficacy of small-molecule transcriptional inhibitors in ATL. View Full-Text
Keywords: super-enhancer; transcription factor; CDK7; CDK9; BRD4; adult T-cell leukemia super-enhancer; transcription factor; CDK7; CDK9; BRD4; adult T-cell leukemia
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Wong, R.W.J.; Ishida, T.; Sanda, T. Targeting General Transcriptional Machinery as a Therapeutic Strategy for Adult T-Cell Leukemia. Molecules 2018, 23, 1057.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top