Next Article in Journal
EpCAM Immunotherapy versus Specific Targeted Delivery of Drugs
Next Article in Special Issue
Advances in Molecular Profiling and Categorisation of Pancreatic Adenocarcinoma and the Implications for Therapy
Previous Article in Journal / Special Issue
Locally Advanced Pancreatic Cancer: A Review of Local Ablative Therapies
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Cancers 2018, 10(1), 14; https://doi.org/10.3390/cancers10010014

Targeting Pancreatic Cancer Cell Plasticity: The Latest in Therapeutics

1
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
2
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 27 December 2017 / Accepted: 4 January 2018 / Published: 10 January 2018
(This article belongs to the Special Issue Latest Development in Pancreatic Cancer)
View Full-Text   |   Download PDF [1791 KB, uploaded 10 January 2018]   |  

Abstract

Mortality remains alarmingly high for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), with 93% succumbing to the disease within five years. The vast majority of PDAC cases are driven by activating mutations in the proto-oncogene KRAS, which results in constitutive proliferation and survival signaling. As efforts to target RAS and its downstream effectors continue, parallel research aimed at identifying novel targets is also needed in order to improve therapeutic options and efficacy. Recent studies demonstrate that self-renewing cancer stem cells (CSCs) contribute to metastatic dissemination and therapy failure, the causes of mortality from PDAC. Here, we discuss current challenges in PDAC therapeutics, highlight the contribution of mesenchymal/CSC plasticity to PDAC pathogenesis, and propose that targeting the drivers of plasticity will prove beneficial. Increasingly, intrinsic oncogenic and extrinsic pro-growth/survival signaling emanating from the tumor microenvironment (TME) are being implicated in the de novo generation of CSC and regulation of tumor cell plasticity. An improved understanding of key regulators of PDAC plasticity is providing new potential avenues for targeting the properties associated with CSC (including enhanced invasion and migration, metastatic outgrowth, and resistance to therapy). Finally, we describe the growing field of therapeutics directed at cancer stem cells and cancer cell plasticity in order to improve the lives of patients with PDAC. View Full-Text
Keywords: cancer stem cells; cell plasticity; epithelial–mesenchymal transition; tumor microenvironment; oncogenes; therapeutics cancer stem cells; cell plasticity; epithelial–mesenchymal transition; tumor microenvironment; oncogenes; therapeutics
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Smigiel, J.M.; Parameswaran, N.; Jackson, M.W. Targeting Pancreatic Cancer Cell Plasticity: The Latest in Therapeutics. Cancers 2018, 10, 14.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top