For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
149
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      556
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.

          Related collections

          Most cited references149

          • Record: found
          • Abstract: found
          • Article: not found

          Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.

          John Neoptolemos, Daniel H Palmer, Paula Ghaneh … (2017)
          The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.
          Article 0 comments Cited 613 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Therapeutic developments in pancreatic cancer: current and future perspectives

            John Neoptolemos, William Greenhalf, Jörg Kleeff … (2018)
            The overall 5-year survival for pancreatic cancer has changed little over the past few decades, and pancreatic cancer is predicted to be the second leading cause of cancer-related mortality in the next decade in Western countries. The past few years, however, have seen improvements in first-line and second-line palliative therapies and considerable progress in increasing survival with adjuvant treatment. The use of biomarkers to help define treatment and the potential of neoadjuvant therapies also offer opportunities to improve outcomes. This Review brings together information on achievements to date, what is working currently and where successes are likely to be achieved in the future. Furthermore, we address the questions of how we should approach the development of pancreatic cancer treatments, including those for patients with metastatic, locally advanced and borderline resectable pancreatic cancer, as well as for patients with resected tumours. In addition to embracing newer strategies comprising genomics, stromal therapies and immunotherapies, conventional approaches using chemotherapy and radiotherapy still offer considerable prospects for greater traction and synergy with evolving concepts.
            Article 0 comments Cited 433 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I

              Keisuke Yamamoto, Anthony Venida, Julian Yano … (2020)
              Immune evasion is a major obstacle for cancer treatment. Common mechanisms include impaired antigen presentation through mutations or loss of heterozygosity (LOH) of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy 1–3 . However, in pancreatic ductal adenocarcinoma (PDAC), a malignancy refractory to most therapies including ICB 4 , mutations causing MHC-I loss are rarely found 5 despite the frequent downregulation of MHC-I expression 6–8 . Here we find that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation through an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced MHC-I cell surface expression and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, autophagy inhibition restores surface MHC-I levels, leading to improved antigen presentation, enhanced anti-tumour T cell response and reduced tumour growth in syngeneic hosts. Accordingly, anti-tumour effects of autophagy inhibition are reversed by depleting CD8+ T cells or reducing surface MHC-I expression. Autophagy inhibition, either genetically or pharmacologically with Chloroquine (CQ), synergizes with dual ICB (anti-PD1 and anti-CTLA4), and leads to an enhanced anti-tumour immune response. Our findings uncover a role for enhanced autophagy/lysosome function in immune evasion through selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB as a therapeutic strategy against PDAC.
              Article 0 comments Cited 414 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 04 July 2020
                Publication date Collection: July 2020
                Volume: 21
                Issue: 13
                Electronic Location Identifier: 4767
                Affiliations
                Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium; camille.huart@ 123456unamur.be (C.H.); jia-wei.chen@ 123456unamur.be (J.-W.C.); benjamin.lecalve@ 123456unamur.be (B.L.C.); carine.michiels@ 123456unamur.be (C.M.)
                Author notes
                [* ]Correspondence: anne-catherine.wera@ 123456unamur.be ; Tel.: +32-81725477
                Author information
                https://orcid.org/0000-0002-9169-1294
                Article
                Publisher ID: ijms-21-04767
                DOI: 10.3390/ijms21134767
                PMC ID: 7369903
                PubMed ID: 32635552
                SO-VID: 28393e5a-3ecc-4f40-a9f8-41373bbc95c2
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 27 May 2020
                Date accepted : 01 July 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: pancreatic cancer,protons,carbon ions,radioresistance,chemoresistance,targeted combination,immunotherapy
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: pancreatic cancer, protons, carbon ions, radioresistance, chemoresistance, targeted combination, immunotherapy

                Comments

                Comment on this article

                scite_

                Similar content556

                See all similar

                Cited by4

                See all cited by

                Most referenced authors3,471

                See all reference authors