Drug Resistance Mechanisms and Tumor Microenvironment in Upper Gastrointestinal Cancers
A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".
Deadline for manuscript submissions: 28 February 2026 | Viewed by 39
Special Issue Editors
Interests: gastroesophageal cancer; immune evasion; drug resistance; biomarker therapies; smoking-induced oncogenesis
Special Issue Information
Dear Colleagues,
Upper gastrointestinal cancers, including gastric and esophageal cancers, are still among the most challenging malignancies to treat, with high morbidity and mortality rates worldwide. Despite significant advancements in cancer therapy, including targeted therapies and immune checkpoint inhibitors, resistance to treatment continues to represent a major hurdle. Understanding the molecular and cellular mechanisms that drive resistance and the complex interactions within the tumor microenvironment is essential in developing more effective therapeutic strategies.
Drug resistance in upper gastrointestinal cancers arises from multiple factors, including genetic mutations, epigenetic modifications, and the activation of compensatory signaling pathways. In addition to intrinsic resistance mechanisms within tumor cells, the tumor microenvironment plays a crucial role in shaping therapeutic responses. Components such as cancer-associated fibroblasts, immune cells, and extracellular matrix elements contribute to a protective niche that enables cancer cells to evade immune surveillance and resist cytotoxic treatments. Emerging evidence suggests that key oncogenic pathways such as Wnt, STAT3, and MYC signaling play critical roles in both tumor progression and resistance to standard therapies. Understanding how these pathways interact with the immune and stromal components of the tumor microenvironment may provide new opportunities for therapeutic intervention.
In recent years, significant progress has been made in identifying novel biomarkers that predict patient responses to therapy. Personalized medicine approaches, including molecular profiling and predictive modeling, are increasingly being utilized to tailor treatments to individual patients, thereby improving clinical outcomes. Preclinical models, such as patient-derived xenografts and organoid cultures, have provided valuable insights into resistance mechanisms and the efficacy of novel drug combinations targeting both tumor cells and their microenvironment.
This Special Issue will highlight recent advances in our understanding of drug resistance mechanisms and the tumor microenvironment in upper gastrointestinal cancers. We welcome original research articles and comprehensive reviews that explore various aspects of this topic, including, but not limited to, molecular and cellular drivers of drug resistance, tumor–stroma interactions and their impact on therapy responses, biomarker discovery and precision medicine strategies, and novel therapeutic approaches targeting the tumor microenvironment. By showcasing cutting-edge research in this area, we hope to advance our understanding of these complex interactions and pave the way for more effective treatments to overcome therapy resistance in upper gastrointestinal cancers.
We invite researchers and clinicians working in this field to contribute their latest findings to this Special Issue, and we look forward to receiving high-quality submissions that will further advance cancer research and therapeutic development.
Dr. Zheng Chen
Dr. Heng Lu
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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
- drug resistance
- tumor microenvironment
- gastric cancer
- esophageal cancer
- immunotherapy
- targeted therapy
- biomarkers
- precision medicine
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