Journal
CANCER TREATMENT REVIEWS
Volume 41, Issue 5, Pages 423-430Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2015.03.006
Keywords
Gastroenteropancreatic neuroendocrine neoplasms; p53; Cancer signaling; Target directed therapy; DNA methylation; DNA damage response
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Funding
- German Theranostics Research Network
- Sonnenfeld Stiftung Berlin
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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous and especially the midgut tumors currently lack effective therapy options. Actionable driver mutations as therapeutic targets are rare. Subtype specific data concerning regulatory mechanisms or epigenetic aberrations are necessary for novel clinical trials. Although the p53 protein itself is rarely mutated in GEP-NENs, epigenetic and regulatory aberrations interfere with the p53 network activity and might function as s target for novel therapeutic approaches. In this review we analyze the current knowledge about the p53 network in GEP-NENs and discuss three possible strategies that include recovering p53 function, enforcing apoptosis by genotoxic stress induction and restoring silenced gene function, based on in vitro, in vivo and clinical data. (C) 2015 Elsevier Ltd. All rights reserved.
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