Translational Insights into Pancreatic Ductal Adenocarcinoma

  • 38k

    Total Downloads

  • 136k

    Total Views and Downloads

Download PDFDownload EPUB

Submit your idea

You will be redirected to our submission process.

Submit your manuscript summarySubmit your manuscript

About this Research Topic

Submission closed

Background

Pancreatic Ductal Adenocarcinoma (PDAC) is now on track to become the second commonest cause of cancer death in the world. Advances in surgery and the development of new chemotherapy regimens have markedly improved survival after surgery for PDAC. However, despite these advances the 5-year survival rate for the majority of unselected patients remains below 9%.

Large scale omics technologies have transformed our understanding of PDAC. These technologies have defined molecular phenotypes (genotypes) that now guide pre-clinical and clinical therapeutic development. Multimodal mapping of PDAC using single cell RNAseq and spatial transcriptomics has identified diverse cell populations resident in tumour samples providing unparalleled insight into PDAC tumour biology.
The development of advanced patient-derived organotypic models and new genetically engineered mouse models (GEMMs) of PDAC is driving the real time translation of emergent drug therapies into the clinic. Patient derived organoids, in particular, are emerging as a pre-eminent model system for PDAC translational research. Grown in 3D scaffolds, these organ-like tumour structures faithfully recapitulate patient sample phenotypes (genotypes) offering a tractable model system for high through-put pharmacogenomics and discovery.

This Research Topic focuses on key aspects of PDAC translational research and how organoids can be utilized to understand complex tumour biology, mechanisms of drug response and for the development/testing of new therapeutic opportunities. The application of emerging organotypic analysis platforms such as organ-on-a-chip platforms, ex vivo tissue culture and high-throughput pharmacogenomic drug screening will be discussed.

A distinguishing feature of PDAC is the abundance of stroma, the collective of non-tumor cells including cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix, and endothelium that exceeds 80% of the tumor mass. Reciprocal signaling between stroma and tumor drives progression, metastasis, therapy resistance and bioavailability of chemotherapeutics. New models that better describe tumor-stroma interaction are required, including how different cellular origins of CAFs result in opposing stromal contributions and outcomes in PDAC. We will describe current advances in organoid-based co-culture model systems for PDAC and their advantages.

Intra-tumoral heterogeneity represents an important clinical challenge, with distinct populations of tumour cells providing a pool of genetic variation that may drive cancer progression and lead to the emergence of drug resistant sub-clones. Advances in genomics are providing new insights into the clonal architecture of PDAC and have defined tumour cell intrinsic phenotypes that exhibit remarkable plasticity. PDAC cells undergo epithelial-mesenchymal transition (EMT) in response to changes in the tumour microenvironment. EMT contributes to drug-resistant clonal expansions, the acquisition of stem cell features and metastatic colonization. Transcription factor networks governing PDAC cell plasticity, EMT, metastasis and drug resistance will be defined, and we will describe how organoid-based models, together with gene editing technologies, can be used to understand and target these transcription factor networks.

Selective targeting of specific immune cell populations and/or immunomodulatory mechanisms (e.g., myeloid cell inhibition and immune checkpoint inhibition) is a promising therapeutic strategy for PDAC. Despite the successful application of immune checkpoint (IC) inhibitors in several cancer types, IC therapies promote marginal responses in PDAC. Mechanisms governing response to immunotherapy and how organoid co-culture systems can be used to develop enhanced strategies for immunotherapy will be discussed. Finally, we will describe how tumour cell intrinsic innate immune pathways contribute to disease progression and how these pathways can be selectively targeted to promote the immune destruction of tumour cells.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and they fall under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

      In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Impact

  • 136kTopic views
  • 96kArticle views
  • 38kArticle downloads
View impact