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Emerging Strategies Targeting Solid Tumors and the Tumor Microenvironment
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Emerging Strategies Targeting Solid Tumors and the Tumor Microenvironment

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 1256

Special Issue Editors

Dr. Emanuela Berrino

E-Mail Website
Guest Editor
Department of Life, Health and Health Professions Sciences, Link Campus University, 00165 Rome, Italy
Interests: carbonic anhydrase inhibitors; carbon monoxide releasing molecules (CORMs); cancer; inflammation; neurodegenerative diseases; drug design
Dr. Giuseppina Catanzaro

E-Mail Website
Guest Editor
Department of Life, Health and Health Professions Sciences, Link Campus University, 00165 Rome, Italy
Interests: cancer cell biology; microRNAs; pediatric brain tumors; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a complex and heterogeneous disease that represents a significant global health burden, being one of the main causes of death worldwide. Despite significant improvements in our understanding of cancer etiology and the markers and cellular mechanisms behind its progression and aggressiveness, cancer remains a significant threat. In recent years, innovative and personalized therapeutic approaches have increased life expectancy for patients with cancer, but continuous efforts from researchers worldwide are still essential to tackling malignancies.

The aim of this Special Issue is to synthesize the latest contributions describing potential new therapeutic approaches to treating cancer. These strategies may include, but are not limited to, small-molecule agents, nanotechnologies, antibody–drug conjugates (ADCs), theragnostic agents, non-coding RNAs and drug repurposing. We are also interested in pharmacological studies aimed at identifying biochemical and metabolic pathways that could potentially be targeted to arrest cancer progression. Both original articles and reviews are welcome.

We believe that this overview of current pharmacological and medicinal chemistry approaches to treating tumor diseases will be of great interest to the scientific community.

We look forward to receiving your contributions!

Dr. Emanuela Berrino
Dr. Giuseppina Catanzaro
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 250 words) can be sent to the Editorial Office for assessment.

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

  • cancer
  • tumor microenvironment
  • medicinal chemistry
  • drug design
  • structure–activity relationships
  • nanotechnologies
  • antibody–drug conjugates
  • non-coding RNAs
  • epigenetic

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Published Papers (2 papers)

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Research

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12 pages, 1528 KB  
Article
Association Between Genomic Features and Radiation Response in Metastatic Breast Cancer Patients Undergoing Palliative Radiotherapy
by Hyeon Seok Choi, Sejoon Lee, So Yeon Park, Jee Hyun Kim, Se Hyun Kim, Koung Jin Suh, Seung Hyuck Jeon and In Ah Kim
Int. J. Mol. Sci. 2025, 26(24), 11837; https://doi.org/10.3390/ijms262411837 - 8 Dec 2025
Viewed by 123
Abstract
Responses to palliative radiotherapy (RT) for metastatic lesions vary among patients, and molecular determinants of radiosensitivity remain unclear. This study investigated genomic features associated with local progression-free survival (LPFS) in metastatic breast cancer patients treated with palliative RT. Forty-four patients who underwent next-generation [...] Read more.
Responses to palliative radiotherapy (RT) for metastatic lesions vary among patients, and molecular determinants of radiosensitivity remain unclear. This study investigated genomic features associated with local progression-free survival (LPFS) in metastatic breast cancer patients treated with palliative RT. Forty-four patients who underwent next-generation sequencing of 523 cancer-related genes were retrospectively analyzed. The biologically effective dose (BED) was calculated using an α/β ratio of 3 Gy, and local progression was defined as recurrence or progression within the irradiated field. A total of 60 metastatic lesions, predominantly in bone (68.3%), were evaluated. Higher BED (≥88 Gy) was significantly associated with longer LPFS (p = 0.011). Among 320 detected mutations mapped to 141 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PI3K–Akt signaling pathway remained an independent predictor in multivariate analysis (p = 0.03). Subgroup analyses demonstrated that patients with Ras, PI3K–Akt, or FoxO pathway mutations derived greater LPFS benefit from high BED, whereas this advantage was confined to wild-type tumors for the PD-L1/PD-1 checkpoint and choline metabolism pathways. These findings suggest that pathway-specific molecular contexts modulate RT response and may inform individualized radiation dose strategies in metastatic breast cancer. Full article
(This article belongs to the Special Issue Emerging Strategies Targeting Solid Tumors and the Tumor Microenvironment)
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Review

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19 pages, 392 KB  
Review
MicroRNAs as Emerging Therapeutic Targets Modulating the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma
by Roxana Daniela Brata, Lavinia Marcut, Alina Cristina Barb, Alexia Manole, Alexandru Ciolofan, Cristina Stefania Dumitru, Flavia Zara and Raul Patrascu
Int. J. Mol. Sci. 2025, 26(21), 10794; https://doi.org/10.3390/ijms262110794 - 6 Nov 2025
Viewed by 900
Abstract
Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive solid tumors, characterized by marked molecular heterogeneity and a complex tumor microenvironment (TME). Recent evidence highlights the pivotal role of microRNAs (miRNAs) in regulating tumor progression, immune evasion, angiogenesis, and [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive solid tumors, characterized by marked molecular heterogeneity and a complex tumor microenvironment (TME). Recent evidence highlights the pivotal role of microRNAs (miRNAs) in regulating tumor progression, immune evasion, angiogenesis, and stromal remodeling. This review synthesizes current insights into miRNA-mediated molecular pathways that modulate the TME in HNSCC and discusses emerging therapeutic strategies, including nanocarrier- and exosome-based miRNA delivery systems, targeting these molecules. Key miRNAs, including miR-21, miR-146a, and miR-221, orchestrate bidirectional signaling between cancer cells, fibroblasts, and immune infiltrates, thereby shaping tumor aggressiveness and therapy resistance. Advances in nanotechnology have facilitated the development of miRNA-based therapeutics—such as mimics, antagomiRs, and exosome-mediated systems—capable of restoring physiological expression patterns and reprogramming the TME toward an anti-tumor state. However, clinical translation remains hindered by challenges in targeted delivery, molecular stability, and tumor heterogeneity. By integrating molecular and translational perspectives, this review underscores how miRNA-targeting strategies may evolve into a new generation of precision therapies, bridging the gap between molecular oncology and personalized treatment of head and neck cancer. Full article
(This article belongs to the Special Issue Emerging Strategies Targeting Solid Tumors and the Tumor Microenvironment)
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