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Biomedicines
Special Issues
Drug Resistance and Tumor Microenvironment in Human Cancers
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Drug Resistance and Tumor Microenvironment in Human Cancers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 March 2026 | Viewed by 4533

Special Issue Editors

Dr. Tiago Miguel Amaral Carvalho

E-Mail Website
Guest Editor
CICS-UBI—Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal
Interests: cancer biology; tumor microenvironment; oncogenic signaling pathways; metabolism; hypoxia; acidosis; drug resistance
Prof. Dr. Silvia Socorro

E-Mail Website
Guest Editor
CICS-UBI—Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal
Interests: cancer biology; cancer metabolism; tumor microenvironment; steroid hormones and receptors; drug resistance
Special Issues, Collections and Topics in MDPI journals
Dr. Marília Isabel Neto Figueira

E-Mail Website
Guest Editor
CICS-UBI—Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal
Interests: cancer biology; estrogens; G protein-coupled estrogen receptor (GPER); tumor microenvironment; drug resistance

Special Issue Information

Dear Colleagues,

We are calling for manuscripts to be published in the Special Issue ‘Drug Resistance and Tumor Microenvironment in Human Cancers’ of the Biomedicines journal.

The tumor microenvironment is a critical contributor to triggering the acquisition of drug resistance. The development of resistance to therapy is a significant barrier to treatment and one of the major challenges in cancer translational research. Understanding the influence of the tumor microenvironment on cancer cell signaling and behavior towards drug resistance is crucial to identify new therapeutic strategies that might increase patients’ survival and life quality. This Special Issue aims to collect and publish recent discoveries on the influence of the tumor microenvironment in cancer drug resistance. Manuscripts describing research on the cellular and molecular basis of resistance to cancer therapy are welcome. Topics may include, but are not limited to, the role of cancer-associated fibroblasts, immune cells, epithelial cells, endothelial cells, acidosis, hypoxia, extracellular matrix proteins and other components of the tumor microenvironment in acquiring drug resistance. Articles identifying novel markers, new therapeutic targets and promising molecular and cellular drug resistance mechanisms will be highly preferred. Original contributions and review articles on this topic are welcomed.

We look forward to receiving your valuable contributions. 

Dr. Tiago Miguel Amaral Carvalho
Prof. Dr. Silvia Socorro
Dr. Marília Isabel Neto Figueira
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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • cancer therapy
  • drug resistance
  • tumor microenvironment
  • targeted therapy
  • precision medicine
  • cancer-related mechanisms

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Published Papers (2 papers)

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Research

27 pages, 17301 KB  
Article
Novel Cross-Cancer Hub Genes in Doxorubicin Resistance Identified by Transcriptional Mapping
by Arseny D. Moralev, Oleg V. Markov, Marina A. Zenkova and Andrey V. Markov
Biomedicines 2025, 13(10), 2527; https://doi.org/10.3390/biomedicines13102527 - 16 Oct 2025
Abstract
Background: Doxorubicin (DOX) is a widely used chemotherapeutic agent, but its efficacy is often limited by cancer cell resistance. Although multiple DOX resistance mechanisms have been characterized, the global transcriptomic alterations underlying this phenomenon remain poorly understood. The aim of this work was [...] Read more.
Background: Doxorubicin (DOX) is a widely used chemotherapeutic agent, but its efficacy is often limited by cancer cell resistance. Although multiple DOX resistance mechanisms have been characterized, the global transcriptomic alterations underlying this phenomenon remain poorly understood. The aim of this work was to determine whether a common transcriptional response associated with DOX desensitization exists across tumor cells of different origins and to identify the core elements of this response. Methods: We performed an integrated bioinformatics analysis, including: analysis of independent transcriptomic datasets (comparing DOX-resistant neuroblastoma, breast, and cervical carcinoma cells to their DOX-sensitive counterparts), functional annotation of differentially expressed genes, reconstruction and topology analysis of gene networks, text mining, and survival analysis. The findings were validated through in vitro functional tests, RT-PCR, and analysis of the Cancer Therapeutics Response Portal and The Cancer Genome Atlas. Results: We showed that DOX resistance in cancer cells is associated with cytoskeletal reorganization, modulation of cell adhesion, cholesterol biosynthesis, and dysregulation of mTORC1, Wnt, and Gβγ signaling pathways. Network analysis identified a conserved regulome of 37 resistance-linked genes, with GJA1, SEH1L, TCF3, TUBA4A, and ZYX emerging as central hubs (mean degree: 8.7–19.7; mean fold change: 2.4–21.3). Experimental validation in DOX-resistant KB-8-5 cervical carcinoma cells and their sensitive counterparts (KB-3-1) confirmed enhanced cellular adhesion and reduced intracellular cholesterol levels associated with chemoresistance, supporting our in silico findings. A detailed follow-up analysis verified the upregulation of these hub genes in chemoresistant cells and their correlation with poor clinical outcomes across multiple cancer types. Conclusions: This integrative analysis identifies conserved transcriptomic signatures of DOX resistance and highlights hub genes GJA1, SEH1L, TCF3, TUBA4A, and ZYX with potential as predictive biomarkers and therapeutic targets. Targeting these pathways may help overcome chemoresistance and improve treatment outcomes in cancer patients. Full article
(This article belongs to the Special Issue Drug Resistance and Tumor Microenvironment in Human Cancers)
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29 pages, 7951 KB  
Article
The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
by Angelica Johansson, Eirini Kalliara, Emma Belfrage, Teodor Alling, Paul Theodor Pyl, Anna Sandström Gerdtsson, Urban Gullberg, Anna Porwit, Kristina Drott and Sara Ek
Biomedicines 2025, 13(1), 186; https://doi.org/10.3390/biomedicines13010186 - 14 Jan 2025
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Abstract
Background/objectives: Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced [...] Read more.
Background/objectives: Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced life expectancy. Today, there is a lack of specific markers for the progression from early to advanced stages of the disease. To address these challenges, the non-interventional BIO-MUSE trial was initiated. Here, we report on a case study involving one patient, where combined omics analysis of tissue and blood was used to reveal the unique molecular features associated with the progression of the disease. Methods: We applied 10× genomics-based single-cell RNA sequencing to CD3+ peripheral T-cells, combined with T-cell receptor sequencing, to samples collected at multiple timepoints during the progression of the disease. In addition, GeoMx-based digital spatial profiling of T-helper (CD3+/CD8−), T-cytotoxic (CD3+/CD8+), and CD163+ cells was performed on skin biopsies. Results. The results pinpoint targets, such as transforming growth factor β1, as some of the mechanisms underlying disease progression, which may have the potential to improve patient prognostication and the development of precision medicine efforts. Conclusions: We propose that in patients with MF, the evolution of the malignant clone and the associated immune response need to be studied jointly to define relevant strategies for intervention. Full article
(This article belongs to the Special Issue Drug Resistance and Tumor Microenvironment in Human Cancers)
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