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Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment—2nd Edition
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Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment—2nd Edition

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 2026 | Viewed by 1158

Special Issue Editor

Dr. Elena Levantini

E-Mail Website
Guest Editor
Consiglio Nazionale delle Ricerche, Istituto di Tecnologie Biomediche, via Moruzzi 1, 56124 Pisa, Italy
Interests: NSCLC; SCLC; murine models; tumor microenvironment; cancer stem cells; therapy resistance; therapeutic targeting; BMI1; scRNAseq; spatial transcriptomics; single-cell interactomes; gene regulation; transcription factors; KRAS; EGFR; miRNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue titled “Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment” (https://www.mdpi.com/journal/ijms/special_issues/B435IC6T8C).

This Special Issue will focus on the intricate molecular mechanisms underlying lung diseases, with a focus on pathogenesis, diagnosis, and treatment. We aim to explore cutting-edge research on lung cancer models, cancer stem cells, and the tumor microenvironment. Key topics include the development and application of targeted therapies, particularly in the context of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).

Our interests span a wide array of molecular and cellular aspects, including the role of BMI1 in cancer stem cell regulation, the use of murine models to study disease progression and resistance to therapy, and the application of single-cell RNA sequencing (scRNAseq) and spatial transcriptomics to uncover novel targeting strategies. We also emphasize the importance of gene regulation, transcription factors, miRNAs, and single-cell interaction networks, as well as KRAS and EGFR mutations, among others, in lung cancer biology.

By bringing these diverse yet interconnected areas of research together, this issue aims to provide a comprehensive overview of the current state of lung disease research and highlight potential personalized medicine options. We invite contributions that offer new perspectives and innovative approaches to understanding and treating lung diseases.

Dr. Elena Levantini
Guest Editor

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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.

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Keywords

  • lung cancer models
  • cancer stem cells
  • tumor microenvironment
  • targeted therapy

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Published Papers (2 papers)

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Research

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21 pages, 2329 KB  
Article
Cross-Disease Breathomics by PTR-TOF-MS: Multiclass Machine Learning and Network Remodeling Across Asthma, COPD, Cystic Fibrosis, and Lymphangioleiomyomatosis
by Malika Mustafina, Artemiy Silantyev, Aleksandr Suvorov, Stanislav Krasovskiy, Marina Makarova, Alexander Chernyak, Olga Suvorova, Anna Shmidt, Daria Gognieva, Aleksandra Bykova, Nana Gogiberidze, Andrei Akselrod, Andrey Belevskiy, Sergey Avdeev, Vladimir Betelin, Abram Syrkin and Philipp Kopylov
Int. J. Mol. Sci. 2026, 27(8), 3483; https://doi.org/10.3390/ijms27083483 - 13 Apr 2026
Viewed by 394
Abstract
Chronic obstructive and inflammatory lung diseases share overlapping clinical manifestations and spirometric features, complicating differential diagnosis and monitoring. In this study, we performed an integrative real-time proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) breathomics analysis to assess whether exhaled volatile organic compound (VOC) profiles enable [...] Read more.
Chronic obstructive and inflammatory lung diseases share overlapping clinical manifestations and spirometric features, complicating differential diagnosis and monitoring. In this study, we performed an integrative real-time proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) breathomics analysis to assess whether exhaled volatile organic compound (VOC) profiles enable multiclass discrimination among bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lymphangioleiomyomatosis (LAM), with healthy individuals as controls. Breath VOC data from 843 subjects were analyzed using a stratified 70/30 train/test split. An ensemble feature selection strategy based on gradient boosting (XGBoost with SMOTE within cross-validation) identified stable VOC panels (top 25% selection probability), yielding 29 VOCs and 31 features including clinical covariates. On the independent test set, the VOC-only model achieved a macro-averaged one-vs-one (OvO) AUC of 0.866 (95% CI 0.829–0.903), while the combined model improved to 0.888 (95% CI 0.853–0.919), indicating modest value of clinical variables. Pairwise analysis demonstrated highest discrimination for CF (AUC up to 0.988), whereas BA and LAM showed lower sensitivity (<0.60), likely reflecting heterogeneity and limited sample size. Given differences in age, sex, BMI, and smoking status across cohorts, confounding effects were assessed, confirming that VOC signatures retain independent diagnostic information. Disease-specific VOC interaction networks revealed distinct remodeling patterns, with central metabolites not captured by univariate analysis. Overall, PTR-TOF-MS breathomics demonstrates proof-of-concept multiclass discrimination across chronic lung diseases. Full article
(This article belongs to the Special Issue Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment—2nd Edition)
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Review

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34 pages, 1683 KB  
Review
Bridging Inflammation and Oncology: The Role and Therapeutic Potential of Macrophage Migration Inhibitory Factor in Lung Cancer
by Mohammed Ali Selo, Oliviero L. Gobbo, Ismael Obaidi, Christine O’Connor, Darren Fayne, Michelle E. Armstrong and Seamas C. Donnelly
Int. J. Mol. Sci. 2026, 27(6), 2829; https://doi.org/10.3390/ijms27062829 - 20 Mar 2026
Viewed by 550
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for more deaths than any other malignancy. Despite advances in treatment, it remains highly lethal, with 5-year survival rates showing minimal improvement over the past several decades, highlighting a critical unmet clinical [...] Read more.
Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for more deaths than any other malignancy. Despite advances in treatment, it remains highly lethal, with 5-year survival rates showing minimal improvement over the past several decades, highlighting a critical unmet clinical need. Macrophage Migration Inhibitory Factor (MIF) is a multifunctional cytokine that contributes to inflammation and cancer, promoting tumor growth, progression, and metastasis through modulation of the tumor microenvironment, stimulation of angiogenesis, and regulation of immune responses. Polymorphisms in the promoter region of MIF, such as high-expression CATT repeats, influence MIF expression and susceptibility to a range of inflammatory, autoimmune, and malignant disorders, yet their role in lung cancer remains largely unexplored. Therapeutic strategies targeting MIF, including small-molecule inhibitors, antibodies, and peptide-based agents, have shown promise in preclinical models, although their clinical translation is still limited. This review discusses the dual role of MIF in inflammation and oncology, summarizes current therapeutic developments, and emphasizes the potential of MIF-targeted interventions in lung cancer. It discusses the significance of genetic predisposition, particularly high-expression MIF alleles, in guiding personalized treatment strategies for lung cancer and identifying patients who may derive benefit from MIF inhibition. Full article
(This article belongs to the Special Issue Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment—2nd Edition)
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