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Targeting Epithelial Mesenchymal Plasticity in Pancreatic Cancer: A Compendium of Preclinical Discovery in a Heterogeneous Disease

1
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia
2
School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4059, Australia
3
Translational Research Institute, Brisbane, QLD 4102, Australia
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(11), 1745; https://doi.org/10.3390/cancers11111745
Received: 8 August 2019 / Revised: 30 October 2019 / Accepted: 30 October 2019 / Published: 7 November 2019
(This article belongs to the Special Issue Metastatic Progression and Tumour Heterogeneity)
Pancreatic Ductal Adenocarcinoma (PDAC) is a particularly insidious and aggressive disease that causes significant mortality worldwide. The direct correlation between PDAC incidence, disease progression, and mortality highlights the critical need to understand the mechanisms by which PDAC cells rapidly progress to drive metastatic disease in order to identify actionable vulnerabilities. One such proposed vulnerability is epithelial mesenchymal plasticity (EMP), a process whereby neoplastic epithelial cells delaminate from their neighbours, either collectively or individually, allowing for their subsequent invasion into host tissue. This disruption of tissue homeostasis, particularly in PDAC, further promotes cellular transformation by inducing inflammatory interactions with the stromal compartment, which in turn contributes to intratumoural heterogeneity. This review describes the role of EMP in PDAC, and the preclinical target discovery that has been conducted to identify the molecular regulators and effectors of this EMP program. While inhibition of individual targets may provide therapeutic insights, a single ‘master-key’ remains elusive, making their collective interactions of greater importance in controlling the behaviours’ of heterogeneous tumour cell populations. Much work has been undertaken to understand key transcriptional programs that drive EMP in certain contexts, however, a collaborative appreciation for the subtle, context-dependent programs governing EMP regulation is needed in order to design therapeutic strategies to curb PDAC mortality. View Full-Text
Keywords: pancreatic cancer; epithelial mesenchymal plasticity; target discovery; review pancreatic cancer; epithelial mesenchymal plasticity; target discovery; review
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MDPI and ACS Style

Monkman, J.H.; Thompson, E.W.; Nagaraj, S.H. Targeting Epithelial Mesenchymal Plasticity in Pancreatic Cancer: A Compendium of Preclinical Discovery in a Heterogeneous Disease. Cancers 2019, 11, 1745. https://doi.org/10.3390/cancers11111745

AMA Style

Monkman JH, Thompson EW, Nagaraj SH. Targeting Epithelial Mesenchymal Plasticity in Pancreatic Cancer: A Compendium of Preclinical Discovery in a Heterogeneous Disease. Cancers. 2019; 11(11):1745. https://doi.org/10.3390/cancers11111745

Chicago/Turabian Style

Monkman, James H.; Thompson, Erik W.; Nagaraj, Shivashankar H. 2019. "Targeting Epithelial Mesenchymal Plasticity in Pancreatic Cancer: A Compendium of Preclinical Discovery in a Heterogeneous Disease" Cancers 11, no. 11: 1745. https://doi.org/10.3390/cancers11111745

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