Review
Version 1
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Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer
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Version 1
: Received: 7 May 2018 / Approved: 8 May 2018 / Online: 8 May 2018 (10:47:27 CEST)
A peer-reviewed article of this Preprint also exists.
Hamdan, F.H.; Johnsen, S.A. Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer. Epigenomes 2018, 2, 8. Hamdan, F.H.; Johnsen, S.A. Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer. Epigenomes 2018, 2, 8.
Abstract
While the mortality rates of cancer are generally declining, pancreatic cancer persists to be an exception with a 5-year-survival rate of less than 7%. Late diagnosis and resistance to conventional therapies contribute to high mortality rates in spite of the remarkable recent advances in cancer management and research. Consequently, there is an urgent need to find new and unconventional therapeutic targets to improve prognosis and survival of pancreatic cancer patients. In this review, we discuss the transcriptional effects of the most widely used epigenetic inhibitors in pancreatic cancer focusing on Bromodomain and Extraterminal domain (BET) and Histone Deacetylase (HDAC) inhibitors, which are currently highly promising therapeutic options. We suggest that these inhibitors can be better utilized at lower doses which exploit their transcriptional modulatory effects on pancreatic cancer transcriptional programs directed by specific factors such as MYC and FOXA1, rather than simply based on their anti-proliferative effects. This approach can potentially help avoid the intolerable adverse events frequently elicited by the use of these treatments at higher doses. In particular, we underscore the crucial role of distal regulatory elements in mediating the specific effects of these epigenetic inhibitors and propose using them in a more selective and prudent manner.
Keywords
BET inhibitors; HDAC inhibitors; pancreatic cancer; aberrant transcription; enhancers; transcription factors; distal regulatory elements; MYC; FOXA1; BRD4
Subject
Medicine and Pharmacology, Gastroenterology and Hepatology
Copyright: 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.
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