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Precision Cancer Medicine: Molecular Insights, Biological Events and Clinical Perspectives
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Precision Cancer Medicine: Molecular Insights, Biological Events and Clinical Perspectives

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: closed (20 June 2026) | Viewed by 2049

Editor

Prof. Dr. Dimitrios H. Roukos

E-Mail Website
Guest Editor
Centre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, Greece
Interests: precision cancer medicine; precision immuno-oncoloy; precision oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Therapeutic resistance and relapse rates remain alarmingly high following standard treatment in cancer patients. The development of meaningful therapy to prevent recurrence in locoregional disease and to substantially improve recurrence-free survival in advanced or metastatic settings remain unmet needs. The advent of multidimensional omics and genome editing technologies at bulk, and particularly at a single-cell resolution, have revolutionized cancer research and therapy over the preceding decade. Patient-specific mutational landscape and tumor molecular profiling have enabled efficient matched targeted therapy. However, prospective validation studies and clinical trials, integrating artificial intelligence and machine learning for the analysis of big standard and multi-omics data, are required to establish precision oncology in clinical practice. The use of high dimensional single-cell multi-omics has resulted in rapid advances in understanding biological events underlying precision immunotherapy including immune checkpoint inhibitors, adoptive T cell therapy and vaccines. The unprecedented capacity of multi-omics, with emphasis on single-cell transcriptome analysis, has uncovered tumor-specific subsets of T cells within the tumor microenvironment. A prime paradigm in the emerging era of precision immuno-oncology represents a pioneering phase I clinical trial, combining individualized mRNA vaccines with atezolizumab and mFOLFIRINOX. In this study, 50% of the patients had an extended period of recurrence-free survival, surpassing 18 months. Ultimately, the deciphering of intratumor molecular and cellular interactions combining spatial transcriptomics with single-cell RNA sequencing is shaping the developmental roadmap towards next-generation tumor systems and network-based therapies.

The present Special Issue, entitled “Precision Cancer Medicine: Molecular Biological Insights”, aims to present recent research developments on Precision Cancer Medicine to those involved in this field and the wider community. We welcome contributions from original articles and reviews which focus on topics within this field.

Prof. Dr. Dimitrios H. Roukos
Guest Editor

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-anonymized 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

  • multi-omics at bulk level
  • single-cell multi-omics
  • precision oncology
  • precision immune-oncology
  • tumor molecular profiling

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Published Papers (2 papers)

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Research

18 pages, 1746 KB  
Article
Genetic Landscape of Lynch Syndrome in a High-Risk Serbian Cohort: Predominance of MLH1 Variants and Implications for Risk-Based Testing
by Marija Djordjic Crnogorac, Valentina Karadzic, Teodora Cato, Milena Cavic, Neda Nikolic, Jelena Spasic, Fedja Djordjevic, Vladimir Jokic, Milan Kocic, Miroslav Djurasinovic, Biljana Kukic, Srdjan Nikolic, Marija Ristic, Marijana Milovic and Ana Krivokuca
Int. J. Mol. Sci. 2026, 27(15), 6652; https://doi.org/10.3390/ijms27156652 (registering DOI) - 25 Jul 2026
Abstract
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline pathogenic or likely pathogenic variants (PV/LPV) in mismatch repair (MMR) genes. Data on the spectrum of LS-associated variants in Slavic populations, including Serbia, remain limited. Given the high [...] Read more.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline pathogenic or likely pathogenic variants (PV/LPV) in mismatch repair (MMR) genes. Data on the spectrum of LS-associated variants in Slavic populations, including Serbia, remain limited. Given the high burden of CRC and endometrial cancer and the limited implementation of hereditary CRC screening, characterizing the spectrum of germline variants in clinically selected high-risk individuals is important for improving genetic testing strategies, risk assessment, and clinical management. Between 2018 and 2025, 176 individuals underwent germline testing for hereditary CRC syndrome based on the Amsterdam/Bethesda criteria, validated LS risk prediction models, and/or family history (FH). Next-generation sequencing (NGS) was performed using the Illumina TruSight Hereditary Cancer Panel, and variants were classified according to American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) guidelines. PV/LPVs in MMR genes were identified in 27/176 (15.3%) and were associated with positive FH of LS-related tumors (p = 0.0001). Most PV/LPVs were identified in MLH1 (10.2%), followed by MSH2 (4.0%) and MSH6 (1.1%), with no PV/LPVs identified in PMS2. Additionally, no pathogenic sequence-level EPCAM variants detectable by the applied panel-based NGS approach were identified. Recurrent MLH1 variants were observed in multiple families, and two previously unreported MLH1 variants were identified. This first systematic analysis of a clinically selected high-risk Serbian cohort provides novel data on the spectrum of LS-associated variants in this referral population, demonstrates the predominance of MLH1 variants, and supports broader implementation of genetic testing, tumor screening, and genetic counseling. Full article
(This article belongs to the Special Issue Precision Cancer Medicine: Molecular Insights, Biological Events and Clinical Perspectives)
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22 pages, 2663 KB  
Article
Modulation of Patient-Derived Tumor Organoids by SARS-CoV-2 Variants Across Cancer Types: A Study Combining Morphology, Inflammation, and Whole-Exome Profiling
by Danielle Ferreira, Tayanne Sassaro, Anael Viana Pinto Alberto, Marília de Melo, Audrien Alves Andrade, Beatriz Iandra Ferreira, Otacílio C. Moreira, Daniel Moreira, Thiago Parente, Bruna Bordim, Júlia de Abreu, Fabiana Rondão, Jorge Canedo, Carlos Gil Ferreira, Elen de Souza, Aline Moreira, Mariana Waghabi, Mariano Gustavo Zalis and Tatiana Tilli
Int. J. Mol. Sci. 2026, 27(3), 1156; https://doi.org/10.3390/ijms27031156 - 23 Jan 2026
Viewed by 962
Abstract
Cancer patients are highly vulnerable to severe COVID-19, requiring models that capture tumor–virus interactions. We investigated tumor- and variant-specific effects of SARS-CoV-2 Gamma and Delta infections using patient-derived organoids (PDOs) from metastatic breast, lung, and colorectal cancers. Viral infection was quantified by Real-Time [...] Read more.
Cancer patients are highly vulnerable to severe COVID-19, requiring models that capture tumor–virus interactions. We investigated tumor- and variant-specific effects of SARS-CoV-2 Gamma and Delta infections using patient-derived organoids (PDOs) from metastatic breast, lung, and colorectal cancers. Viral infection was quantified by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) 24 h post-infection, and morphological changes and immune mediators were profiled. Genomic analysis using whole-exome sequencing was performed to identify contributing host-related gene alterations. The Delta variant produced consistently higher viral loads in lung and breast PDOs, while colorectal PDOs showed variable susceptibility. Infection led to reduced area and perimeter and increased circularity across all tumor types. Immune profiling revealed distinct responses: Gamma decreased Interferon alpha (IFNα) in lung PDOs and increased E-selectin in colorectal PDOs. Delta broadly reduced inflammatory mediators in lung [10 kDa interferon gamma-induced protein (IP-10) and Intercellular adhesion molecule 1 (ICAM-1)] and breast [Interleukin-6 (IL-6), Interleukin-13 (IL-13), and Interleukin-17A (IL-17A)] PDOs, while increasing Macrophage inflammatory protein 1-beta (MIP-1β) in colorectal PDOs. Host gene variants involved in trafficking (FYCO1 and RAB7A) and immune signaling (FOXA2, SFTPD, STAT3, and TET2) were associated with differential infection profiles. These findings show that SARS-CoV-2 induces variant- and tumor-specific morphological and immunological changes in cancer PDOs, highlighting the potential of this model to unravel host–virus interactions and identify genetic factors that shape infection outcomes in cancer. Full article
(This article belongs to the Special Issue Precision Cancer Medicine: Molecular Insights, Biological Events and Clinical Perspectives)
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