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25th Anniversary of IJMS: Updates and Advances in Molecular Oncology

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 December 2025 | Viewed by 2542

Special Issue Editor

Dr. Peter J. K. Kuppen

E-Mail Website
Guest Editor
Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Interests: colorectal cancer; tumor-immmune interactions; cancer genetics and epigenetics; immunotherapy; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer research entered a new molecular era at the turn of the 21st century: the full sequence of the human genome was just published, and genomic sequencing became standard practice and is now even part of routine clinical diagnostics. Today, as we celebrate the journal’s 25th anniversary, we reflect not only on its growth and accomplishments but also on the remarkable journey of cancer research, which the journal has documented and helped shape. Our understanding of cancer biology has deepened from single-gene models to complex networks involving epigenetics, tumour heterogeneity, the tumour microenvironment, and interactions with the immune system. This has led to whole new cancer treatment options and improved diagnostics, all leading to much better prospects for current cancer patients.

This anniversary Special Issue intends to bring together a collection of articles that reflect on the journal’s legacy while highlighting key advances that are currently redefining the field. We invite long-standing leaders and emerging voices, all of whom share a commitment to rigorous science and translational impact, to contribute to this special issue. Together, these pieces provide both a retrospective lens and a forward-looking perspective on the challenges and opportunities that lie ahead of us.

Among the highlights of this issue are reviews and original studies covering diverse and pressing topics: the evolving role of precision oncology, the promise and limitations of liquid biopsy technologies, advances in cancer immunotherapy, the rise of AI and digital pathology, and novel insights into the molecular mechanisms of tumour development. Each contribution will be selected not only for its scientific merit but also for its relevance to the journal’s mission of connecting the bench and bedside.

We also recognize that the future of molecular oncology demands continued collaboration across disciplines, sectors, and continents. As cancer remains one of the most complex and urgent health challenges of our time, the integration of molecular insights with clinical practice remains as critical today as it was 25 years ago. With this in mind, Molecular Oncology will continue to serve as a platform for work that not only advances knowledge but also catalyses real-world progress.

We invite you to contribute to this Special Issue, reflect on the progress we have made together, and join us in shaping the next 25 years of molecular oncology all for our shared pursuit of better cancer care.

Dr. Peter J. K. Kuppen
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 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. 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

  • molecular oncology
  • cancer epigenetics
  • tumour heterogeneity
  • tumour microenvironment
  • precision oncology
  • liquid biopsy
  • cancer immunotherapy

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Published Papers (5 papers)

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Research

Jump to: Review

17 pages, 5865 KB  
Article
Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA
by Marina Danilenko, Sharanya Nath, Jack Baines, Freya Gordon, Swathi Merugu, Lisa M. Allinson, Aaron Potts, Bethany Collins, Angharad Goodman, Samuel E. Kidman, Ciaron McAnulty, David Jamieson and Deborah A. Tweddle
Int. J. Mol. Sci. 2025, 26(19), 9466; https://doi.org/10.3390/ijms26199466 - 27 Sep 2025
Abstract
Neuroblastoma (NB) is an aggressive childhood cancer requiring intensive multimodal therapies in high-risk (HRNB) patients. Currently, invasive surgical biopsies are required to classify NB risk group and assign treatment based on the tumour genetic profile. Circulating tumour DNA (ctDNA) obtained from blood samples [...] Read more.
Neuroblastoma (NB) is an aggressive childhood cancer requiring intensive multimodal therapies in high-risk (HRNB) patients. Currently, invasive surgical biopsies are required to classify NB risk group and assign treatment based on the tumour genetic profile. Circulating tumour DNA (ctDNA) obtained from blood samples can be used to identify tumour biomarkers. Here we applied targeted next-generation sequencing (tNGS) using a panel of 42 genes to analyse 32 NB ctDNA samples for the presence of single-nucleotide variants and copy number changes from 28 patients in all NB risk groups. In two additional ctDNA samples, droplet digital PCR was used to detect hotspot ALK variants. Pathogenic mutations with a variant allele frequency (VAF) > 1% were identified in 13/32 (41%) ctDNA samples. ALK and PTPN11 were the most frequent, each being detected in 4/32 (13%) samples, together with oncogene amplifications. Targeted NGS of ctDNA detected actionable variants, including those absent in the diagnostic primary tumour due to spatial and temporal heterogeneity. Our findings confirm the usefulness of ctDNA in detecting genetic abnormalities in NB. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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16 pages, 3324 KB  
Article
The Role of MICA/B Molecules and the NKG2D Receptor in the Interaction Between NK-92 Cells and JEG-3 Cells
by Elizaveta Tyshchuk, Elizaveta Denisova, Polina Grebenkina, Marina Pereviazkina, Anastasia Stolbovaya, Ilya Smirnov, Olga Shashkova, Irina Gryazeva, Lidiya Terekhina and Dmitry Sokolov
Int. J. Mol. Sci. 2025, 26(17), 8400; https://doi.org/10.3390/ijms26178400 - 29 Aug 2025
Viewed by 412
Abstract
MICA/B molecules (MICs) are stress-induced molecules expressed by infected and tumor cells. Their expression also characterizes trophoblast cells. Cytotoxic lymphocytes, including natural killer (NK) cells, express the NKG2D receptor, aiding them in the recognition and destruction of target cells that present MICs. To [...] Read more.
MICA/B molecules (MICs) are stress-induced molecules expressed by infected and tumor cells. Their expression also characterizes trophoblast cells. Cytotoxic lymphocytes, including natural killer (NK) cells, express the NKG2D receptor, aiding them in the recognition and destruction of target cells that present MICs. To evade destruction, target cells employ various defense mechanisms, including the secretion of soluble forms of MICs. Choriocarcinoma JEG-3 cells and NK-92 cells were used to assess the expression of MICs and NKG2D. The cytotoxicity of NK-92 cells against JEG-3 cells in the presence of trichostatin A (TSA), anti-MICA/B antibodies (anti-MICA/B), and recombinant MIC proteins (rMICA/B) was evaluated. JEG-3 cells and NK-92 cells express MICs. Additionally, NK-92 cells exhibit high levels of NKG2D receptor expression. TSA treatment reduced the surface expression of MICs on choriocarcinoma cells, and was also associated with the release of soluble MICB. However, the TSA-induced decrease in MIC expression by choriocarcinoma cells did not protect them from the cytotoxic effects of NK cells. Only the activation of NK cells by IL-12 resulted in a decline in susceptibility of TSA-treated choriocarcinoma cells to NK cell-mediated cytotoxicity. Thus, NK cells activated by IL-12 lose their ability to effectively kill TSA-treated choriocarcinoma cells through the MIC-mediated mechanisms. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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Review

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16 pages, 512 KB  
Review
CAR-T in the Treatment of Solid Tumors—A Review of Current Research and Future Perspectives
by Natalia Picheta, Julia Piekarz, Karolina Daniłowska, Katarzyna Szklener and Sławomir Mańdziuk
Int. J. Mol. Sci. 2025, 26(19), 9486; https://doi.org/10.3390/ijms26199486 - 28 Sep 2025
Abstract
The aim of this narrative review is to present the current state of knowledge regarding the use of chimeric antigen receptor T-cell (CAR-T) therapy in solid tumors. Phase I clinical trials and side effects are discussed. The review is based on an analysis [...] Read more.
The aim of this narrative review is to present the current state of knowledge regarding the use of chimeric antigen receptor T-cell (CAR-T) therapy in solid tumors. Phase I clinical trials and side effects are discussed. The review is based on an analysis of available scientific publications, primarily phase I trials, Food and Drug Administration (FDA) reports, and PubMed, Scopus, and Google Scholar sources. It includes clinical trials and review articles from 2016 to 2025. Accumulated data indicate promising efficacy of CAR-T therapy in the treatment of certain solid tumors, particularly those of the gastrointestinal tract, although clinical responses were often limited to disease stabilization. The therapy was generally well tolerated, with a low incidence of serious adverse events. Efficacy was found to depend on factors such as the type of target antigen, the presence of conditioning therapy, and the ability to overcome the immunosuppressive tumor microenvironment. CAR-T therapy remains experimental outside of hematological malignancies, but further development, refinement of receptor design, and the search for better molecular targets may make it an effective treatment option for solid tumors as well. Current studies are in early phase and require confirmation in larger-scale randomized trials. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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18 pages, 946 KB  
Review
TIGIT Expression and Its Implications in Non-Small-Cell Lung Cancer Progression and Therapy: A Systematic Review
by Julia Piekarz, Natalia Picheta, Katarzyna Szklener and Sławomir Mańdziuk
Int. J. Mol. Sci. 2025, 26(19), 9307; https://doi.org/10.3390/ijms26199307 - 23 Sep 2025
Viewed by 152
Abstract
Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) representing 85–90% of cases. Despite the efficacy of PD-1/PD-L1 immune checkpoint inhibitors, primary and acquired resistance highlight the need for novel immunotherapeutic strategies. A systematic review of [...] Read more.
Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) representing 85–90% of cases. Despite the efficacy of PD-1/PD-L1 immune checkpoint inhibitors, primary and acquired resistance highlight the need for novel immunotherapeutic strategies. A systematic review of the literature from 2020 to 2025 was conducted according to the PICO model. Six studies were included, encompassing phase I–III clinical trials. The analysis focused on efficacy, safety, and emerging therapeutic strategies targeting TIGIT in NSCLC. TIGIT blockade enhances cytotoxic T lymphocyte and natural killer (NK) cell activity, strengthening antitumor immunity. Clinical trials, particularly with the monoclonal antibody tiragolumab combined with PD-1/PD-L1 inhibitors, show promising synergistic effects. Emerging strategies, including bispecific antibodies (e.g., TIGIT/PD-1 and TIGIT/PD-L1) and experimental cell therapies, are under investigation to further improve the antitumor response. Anti-TIGIT therapies represent a highly promising approach in NSCLC. While phase III data remain limited, biomarker-driven, well-designed trials are essential. If validated, TIGIT blockade could become a key addition to immuno-oncology treatment strategies for NSCLC. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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36 pages, 3285 KB  
Review
Cold, Hot, and Lethal—The Tumour Microenvironment and the Immunology of Head and Neck Squamous Cell Carcinoma
by Svatava Vyhnánková, Lukáš Lacina, Martin Chovanec, Jan Plzák, Karel Smetana, Jr., Jiří Netušil, Michal Kolář and Radek Šindelka
Int. J. Mol. Sci. 2025, 26(18), 8844; https://doi.org/10.3390/ijms26188844 - 11 Sep 2025
Viewed by 450
Abstract
Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. [...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME—mediated by cytokines such as IL-6, TGF-b, and galectins—further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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