Association of epigenetic landscapes with heterogeneity and plasticity in pancreatic cancer.

Autor: Manoukian P; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands. Electronic address: p.manoukian@amsterdamumc.nl., Kuhnen LC; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands., van Laarhoven HWM; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands., Bijlsma MF; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology, Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: Critical reviews in oncology/hematology [Crit Rev Oncol Hematol] 2024 Nov 22; Vol. 206, pp. 104573. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1016/j.critrevonc.2024.104573
Abstrakt: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.
Competing Interests: Declaration of Competing Interest MFB has received research funding from Celgene, Frame Therapeutics, and Lead Pharma, and has acted as a consultant to Servier, Olympus and Wholomics. HWML Consultant or advisory role: Amphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, Daiichy-Sankyo, Dragonfly, MSD, Myeloid, Servier Research funding, medication supply, and/or other research support: Auristone, Incyte, Merck, ORCA, Servier. Speaker role: Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management B.V. JWW Consultant or advisory role: MSD, Servier, Astra Zeneca, Research funding: MSD, Nordic, Servier. Speaker role: MSD, Servier. None of these parties participated in the design or drafting of the manuscript.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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