Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment

Asmaa Elrakaybi; Dietrich A. Ruess; Michael Lübbert; Michael Quante; Heiko Becker

doi:10.3390/cancers14235926

Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment

Asmaa Elrakaybi, Dietrich A. Ruess, Michael Lübbert, Michael Quante, Heiko Becker

Research output: Contribution to journal › Review article › peer-review

7 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.

Original language	English
Article number	5926
Journal	Cancers
Volume	14
Issue number	23
DOIs	https://doi.org/10.3390/cancers14235926
State	Published - Dec 2022
Externally published	Yes

Keywords

BET inhibitors
DNMT inhibitors
EZH2 inhibitors
HDAC inhibitors
cfDNA methylation
epigenetics
pancreatic ductal adenocarcinoma
retinoids

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14235926

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title = "Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.",

keywords = "BET inhibitors, DNMT inhibitors, EZH2 inhibitors, HDAC inhibitors, cfDNA methylation, epigenetics, pancreatic ductal adenocarcinoma, retinoids",

author = "Asmaa Elrakaybi and Ruess, {Dietrich A.} and Michael L{\"u}bbert and Michael Quante and Heiko Becker",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = dec,

doi = "10.3390/cancers14235926",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "23",

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TY - JOUR

T1 - Epigenetics in Pancreatic Ductal Adenocarcinoma

T2 - Impact on Biology and Utilization in Diagnostics and Treatment

AU - Elrakaybi, Asmaa

AU - Ruess, Dietrich A.

AU - Lübbert, Michael

AU - Quante, Michael

AU - Becker, Heiko

PY - 2022/12

Y1 - 2022/12

N2 - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.

AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.

KW - BET inhibitors

KW - DNMT inhibitors

KW - EZH2 inhibitors

KW - HDAC inhibitors

KW - cfDNA methylation

KW - epigenetics

KW - pancreatic ductal adenocarcinoma

KW - retinoids

UR - http://www.scopus.com/inward/record.url?scp=85143632188&partnerID=8YFLogxK

U2 - 10.3390/cancers14235926

DO - 10.3390/cancers14235926

M3 - Review article

AN - SCOPUS:85143632188

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 23

M1 - 5926

ER -

Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment

Abstract

Keywords

UN SDGs

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