Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer
AbstractWhile 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 Forkhead Box A1 (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. View Full-Text
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Hamdan, F.H.; Johnsen, S.A. Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer. Epigenomes 2018, 2, 8.
Hamdan FH, Johnsen SA. Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer. Epigenomes. 2018; 2(2):8.Chicago/Turabian Style
Hamdan, Feda H.; Johnsen, Steven A. 2018. "Epigenetic Targeting of Aberrant Transcriptional Modulation in Pancreatic Cancer." Epigenomes 2, no. 2: 8.
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