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IJMS
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Molecular Pathology and New Potential Targeted Therapies in Gastrointestinal Cancers
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Molecular Pathology and New Potential Targeted Therapies in Gastrointestinal Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 654

Special Issue Editors

Dr. Laura Georgiana Necula

E-Mail Website
Guest Editor
Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania
Interests: viral mechanisms; immune evasion; targeted therapy; biomarkers for early diagnosis
Special Issues, Collections and Topics in MDPI journals
Dr. Mihaela Chivu-Economescu

E-Mail Website
Guest Editor
Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania
Interests: immuno-oncology; biomarkers to predict responsiveness to therapy; innate mechanisms of resistance to therapy

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our Special Issue of the International Journal of Molecular Sciences (IJMS), entitled “Molecular Pathology and New Potential Targeted Therapies in Gastrointestinal Cancers”. This Research Topic aims to gather the latest research and ideas on innovative approaches to exploit for clinical and therapeutic purposes the molecular mechanisms involved in the development of gastrointestinal cancer. We welcome papers that address the progress that has been made in understanding the molecular pathogenesis of gastrointestinal cancers, and the discovery of new potential biomarkers for early diagnosis or progression, that can be used as therapeutic targets for these malignancies. We are also interested in papers that investigate recent advances in the field of combinations of targeted and immunotherapy to overcome clinical resistance in cancer, and development of predictive biomarkers that may improve effective evaluation of these therapies.

This Special Issue is now open for submissions. If you are interested in contributing your work, please send a short abstract or tentative title to the Guest Editors or Editorial Office.

Dr. Laura Georgiana Necula
Dr. Mihaela Chivu-Economescu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal cancers
  • molecular pathology
  • tumor microenvironment
  • targeted therapy
  • immunotherapy
  • biomarkers
  • cancer resistance

Published Papers (1 paper)

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Research

19 pages, 3969 KiB  
Article
Cytokine CCL9 Mediates Oncogenic KRAS-Induced Pancreatic Acinar-to-Ductal Metaplasia by Promoting Reactive Oxygen Species and Metalloproteinases
by Geou-Yarh Liou, Crystal J. Byrd, Peter Storz and Justin K. Messex
Int. J. Mol. Sci. 2024, 25(9), 4726; https://doi.org/10.3390/ijms25094726 - 26 Apr 2024
Viewed by 242
Abstract
Pancreatic ductal adenocarcinoma (PDAC) can originate from acinar-to-ductal metaplasia (ADM). Pancreatic acini harboring oncogenic Kras mutations are transdifferentiated to a duct-like phenotype that further progresses to become pancreatic intraepithelial neoplasia (PanIN) lesions, giving rise to PDAC. Although ADM formation is frequently observed in [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) can originate from acinar-to-ductal metaplasia (ADM). Pancreatic acini harboring oncogenic Kras mutations are transdifferentiated to a duct-like phenotype that further progresses to become pancreatic intraepithelial neoplasia (PanIN) lesions, giving rise to PDAC. Although ADM formation is frequently observed in KrasG12D transgenic mouse models of PDAC, the exact mechanisms of how oncogenic KrasG12D regulates this process remain an enigma. Herein, we revealed a new downstream target of oncogenic Kras, cytokine CCL9, during ADM formation. Higher levels of CCL9 and its receptors, CCR1 and CCR3, were detected in ADM regions of the pancreas in p48cre:KrasG12D mice and human PDAC patients. Knockdown of CCL9 in KrasG12D-expressed pancreatic acini reduced KrasG12D-induced ADM in a 3D organoid culture system. Moreover, exogenously added recombinant CCL9 and overexpression of CCL9 in primary pancreatic acini induced pancreatic ADM. We also showed that, functioning as a downstream target of KrasG12D, CCL9 promoted pancreatic ADM through upregulation of the intracellular levels of reactive oxygen species (ROS) and metalloproteinases (MMPs), including MMP14, MMP3 and MMP2. Blockade of MMPs via its generic inhibitor GM6001 or knockdown of specific MMP such as MMP14 and MMP3 decreased CCL9-induced pancreatic ADM. In p48cre:KrasG12D transgenic mice, blockade of CCL9 through its specific neutralizing antibody attenuated pancreatic ADM structures and PanIN lesion formation. Furthermore, it also diminished infiltrating macrophages and expression of MMP14, MMP3 and MMP2 in the ADM areas. Altogether, our results provide novel mechanistic insight into how oncogenic Kras enhances pancreatic ADM through its new downstream target molecule, CCL9, to initiate PDAC. Full article
(This article belongs to the Special Issue Molecular Pathology and New Potential Targeted Therapies in Gastrointestinal Cancers)
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