Next Article in Journal
When a Slice Is Not Enough! Comparison of Whole-Brain versus Standard Limited-Slice Perfusion Computed Tomography in Patients with Severe Traumatic Brain Injury
Next Article in Special Issue
Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure
Previous Article in Journal
Factors for the Early Revision of Misdiagnosed Tuberculosis to Lung Cancer: A Multicenter Study in A Tuberculosis-Prevalent Area
Previous Article in Special Issue
XPO1 Expression Is a Poor-Prognosis Marker in Pancreatic Adenocarcinoma
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessReview

Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks

1
Laboratory of Advanced Molecular Therapeutics, Division of Gastroenterology, Department of Internal Medicine, Integrative Therapy Center for Gastroenterologic Cancers, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
2
Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan
4
Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion Integrated Cancer Center, Technion—Israel Institute of Technology, Haifa 3525433, Israel
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 702; https://doi.org/10.3390/jcm8050702
Received: 27 April 2019 / Revised: 8 May 2019 / Accepted: 15 May 2019 / Published: 17 May 2019
  |  
PDF [3556 KB, uploaded 17 May 2019]
  |     |  

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating and highly aggressive malignancy. Existing therapeutic strategies only provide a small survival benefit in patients with PDAC. Laboratory and clinical research have identified various populations of stem-cell-like cancer cells or cancer stem cells (CSCs) as the driving force of PDAC progression, treatment-resistance, and metastasis. Whilst a number of therapeutics aiming at inhibiting or killing CSCs have been developed over the past decade, a series of notable clinical trial setbacks have led to their deprioritization from the pipelines, triggering efforts to refine the current CSC model and exploit alternative therapeutic strategies. This review describes the current and the evolving models of pancreatic CSCs (panCSCs) and the potential factors that hamper the clinical development of panCSC-targeted therapies, emphasizing the heterogeneity, the plasticity, and the non-binary pattern of cancer stemness, as well as the desmoplastic stroma impeding drug penetration. We summarized novel and promising therapeutic strategies implicated by the works of our groups and others’ that may overcome these hurdles and have shown efficacies in preclinical models of PDAC, emphasizing the unique advantages of targeting the stroma-engendered panCSC-niches and metronomic chemotherapy. Finally, we proposed feasible clinical trial strategies and biomarkers that can guide the next-generation clinical trials. View Full-Text
Keywords: cancer stemness; pancreatic ductal adenocarcinoma; stroma; therapeutics; clinical trials cancer stemness; pancreatic ductal adenocarcinoma; stroma; therapeutics; clinical trials
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

Tsai, K.K.; Chan, T.-S.; Shaked, Y. Next Viable Routes to Targeting Pancreatic Cancer Stemness: Learning from Clinical Setbacks. J. Clin. Med. 2019, 8, 702.

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]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top