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Cancers, Volume 17, Issue 12 (June-2 2025) – 5 articles

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18 pages, 1937 KiB  
Article
Applications for Circulating Cell-Free DNA in Oral Squamous Cell Carcinoma: A Non-Invasive Approach for Detecting Structural Variants, Fusions, and Oncoviruses
by Mahua Bhattacharya, Dan Yaniv, Dylan P. D’Souza, Eyal Yosefof, Sharon Tzelnick, Rajesh Detroja, Tal Wax, Adva Levy-Barda, Gideon Baum, Aviram Mizrachi, Gideon Bachar and Milana Frenkel Morgenstern
Cancers 2025, 17(12), 1901; https://doi.org/10.3390/cancers17121901 - 6 Jun 2025
Abstract
Background: Circulating cell-free DNA (cfDNA) has been widely used as a prognostic marker for different cancers. Objective: In this study, we used 30 cfDNA samples from oral squamous cell carcinoma (OSCC), 199 public OSCC samples, and 192 normal samples to study various [...] Read more.
Background: Circulating cell-free DNA (cfDNA) has been widely used as a prognostic marker for different cancers. Objective: In this study, we used 30 cfDNA samples from oral squamous cell carcinoma (OSCC), 199 public OSCC samples, and 192 normal samples to study various correlation factors that could improve the early-stage diagnostics and/or prognosis of OSCC. Methods: The statistical correlation between healthy and OSCC patients was done and deep sequencing analyses was performed to study various genomic alterations likes copy number variation (CNV), and single nucleotide variants (SNVs), gene fusion and genomic integration of viruses. Results: We found that the OSCC patient cfDNA concentration can serve as an indicator of tumor stage, malignancy, and survival prognosis. Deep genome sequencing of cfDNA revealed genomic alterations, such as CNVs, fusion genes, and viral integrations. The CNV analysis suggested a correlation with amplification and deletion in chromosomes at loci 1q, 2q, 3p, 3q, and chromosome 8 at loci q22. Moreover, at these loci, amplification of TP53, PIK3CA, and other genes related to keratinization in OSCC patients was observed. In addition, we identified a novel abundant fusion gene, TRMO-TRNT1 ‘chimera’, in seven high-grade tumor samples. The parental genes of this chimera, TRMO and TRNT1, are known to play roles in tRNA modification and DNA repair, respectively. We have identified SNVs in our OSCC cohort. Some of these SNVs, like KMT2C, MUC3A, and MUC6, have been identified as common cases in different cancer populations. Finally, we detected contigs integrations of human papillomavirus, simian virus, and enterovirus in the OSCC samples, which may point to the potential causes of OSCC. Conclusions: Our results indicate that the liquid biopsy technique may thus serve as a sensitive tool to study OSCC patient genomic alterations by exploring cfDNA circulating in the plasma, providing an easy-to-use blood test in the future. Full article
(This article belongs to the Special Issue Circulating Tumour DNA and Liquid Biopsy in Oncology)
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22 pages, 920 KiB  
Review
Perineural Invasion in Breast Cancer: A Comprehensive Review
by Hisham F. Bahmad, Carter Wegner, Joana Nuraj, Rima Avellan, Jeffrey Gonzalez, Teresita Mendez, Diana Jabbour and Carmen Gomez-Fernandez
Cancers 2025, 17(12), 1900; https://doi.org/10.3390/cancers17121900 - 6 Jun 2025
Abstract
Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and [...] Read more.
Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and clinical relevance. PNI is most frequently observed in high-grade invasive ductal carcinoma (IDC), particularly in triple-negative and HER2-positive subtypes. It is also seen in special histological subtypes such as mixed, metaplastic, and invasive micropapillary carcinomas. Mechanistically, PNI involves tumor–neural interactions, including neurotrophic factor signaling and epithelial–mesenchymal transition, contributing to tumor progression and potential locoregional recurrence (LRR). While PNI is linked to adverse prognosis in other tumors, its independent role remains unclear in breast cancer due to limited large-scale studies. Therefore, further investigation into its prognostic significance and potential therapeutic implications is needed. Future research should focus on refining diagnostic criteria and assessing targeted therapies to mitigate PNI-associated progression. This review summarizes the current knowledge on perineural invasion (PNI) in breast cancer, addressing its histological features, molecular mechanisms, diagnostic challenges, and clinical implications. Full article
(This article belongs to the Section Cancer Pathophysiology)
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23 pages, 1338 KiB  
Review
Advancing Precision Medicine in PDAC: An Ethical Scoping Review and Call to Action for IHC Implementation
by Lyanne A. Delgado-Coka, Lucia Roa-Peña, Andrew Flescher, Luisa F. Escobar-Hoyos and Kenneth R. Shroyer
Cancers 2025, 17(12), 1899; https://doi.org/10.3390/cancers17121899 - 6 Jun 2025
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, prevention, and treatment. Predictive biomarkers offer the potential to revolutionize clinical management, particularly in the preoperative setting, but their implementation requires careful consideration of ethical implications. This scoping review analyzes the ethical landscape of [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, prevention, and treatment. Predictive biomarkers offer the potential to revolutionize clinical management, particularly in the preoperative setting, but their implementation requires careful consideration of ethical implications. This scoping review analyzes the ethical landscape of using immunohistochemistry (IHC) for molecular subtyping in PDAC, focusing on its utility, accessibility, and potential impact on patient care. We conducted a systematic literature search in the PubMed, Scopus and Google Scholar databases (2015–2025) using COVIDENCE, which identified 130 references. Of these, 79 were reviewed in a full-text format, and 9 ultimately met the inclusion criteria for our analysis. IHC offers several advantages as a companion diagnostic tool. It is relatively inexpensive, widely available in most pathology laboratories, and can be readily integrated into existing clinical workflows. This contrasts with more complex molecular subtyping methods, such as gene expression profiling, which can be costly, require specialized equipment and expertise, and may not be readily accessible in all clinical settings. Furthermore, accurate analysis of gene expression requires the localized targeting of individual cells; therefore, digesting the sample for bulk analysis would be less informative than using spatial localization techniques such as IHC. Because biomarker regulation can occur at the level of transcription or translation, protein-level assessment via IHC is often more accurate than mRNA analysis. Standardized IHC protocols for biomarker assessment are therefore essential for translating the molecular subtyping of PDAC into clinically actionable treatment strategies, especially for aggressive subtypes like basal-like tumors. This readily deployable IHC-based approach can optimize therapy selection, maximizing patient benefits and minimizing exposure to ineffective and potentially toxic treatments. This review critically analyzes the ethical dimensions of this method, grounded in the principles of autonomy, beneficence, non-maleficence, and justice. The review urges the medical community to fully utilize the potential of IHC-driven molecular subtyping to improve outcomes in PDAC, while ensuring equitable and responsible access to the benefits of precision oncology for all patients. Full article
(This article belongs to the Special Issue Management of Pancreatic Cancer)
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17 pages, 494 KiB  
Review
The Impact of Social Determinants on Pancreatic Cancer Care in the United States
by Shreeja N. Patel, Joseph R. Habib, Daniel Brock Hewitt, Michael D. Kluger, Katherine Morgan, Ammar A. Javed, Christopher L. Wolfgang and Greg D. Sacks
Cancers 2025, 17(12), 1898; https://doi.org/10.3390/cancers17121898 - 6 Jun 2025
Abstract
With a rising annual incidence, pancreatic cancer is now the third leading cause of cancer-related mortality in American men and women [...] Full article
(This article belongs to the Special Issue Impact of Social Determinants on Cancer Care)
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16 pages, 2086 KiB  
Article
Comparative Analysis of Clinical Outcomes in High-Grade Glioma Patients: 5-ALA Fluorescence-Guided Surgery vs. Conventional White-Light Resection
by Nurzhan Ryskeldiyev, Aidos Moldabekov, Dinara Berdibayeva, Aiman Maidan, Torebek Tursynbekov, Dimash Davletov, Muratbek Tleubergenov, Assel Kabykenova, Diana Kerimbayeva, Aidos Doskaliyev and Serik Akshulakov
Cancers 2025, 17(12), 1897; https://doi.org/10.3390/cancers17121897 - 6 Jun 2025
Abstract
Background High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses. Maximizing the extent of resection (EOR) is a critical surgical goal. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been proposed to enhance tumor visualization and resection. MethodsWe retrospectively analyzed 141 patients with [...] Read more.
Background High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses. Maximizing the extent of resection (EOR) is a critical surgical goal. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been proposed to enhance tumor visualization and resection. MethodsWe retrospectively analyzed 141 patients with histologically confirmed HGGs who underwent either 5-ALA-guided (n = 71) or conventional white-light (n = 70) resection between 2018 and 2023. Propensity score matching and multivariate Cox regression models were used to assess the impact of 5-ALA on surgical outcomes and survival. Results: Gross total resection (GTR) was significantly more common in the 5-ALA group than the conventional white-light group (28.17% vs. 12.86%, p = 0.0245). Kaplan–Meier analysis showed no statistically significant difference in overall survival between groups after matching (log-rank p = 0.6371). However, patients with GTR had significantly improved survival compared to those with subtotal resection (log-rank p = 0.0423). Multivariate Cox regression identified radiotherapy (HR = 0.291, 95% CI: 0.166–0.513, p < 0.001), higher Karnofsky Performance Status (HR = 0.962, 95% CI: 0.942–0.982, p = 0.0003), and GTR (HR = 0.476, 95% CI: 0.272–0.834, p = 0.0091) as independent predictors of improved survival. 5-ALA usage was not an independent predictor (HR = 0.885, 95% CI: 0.554–1.413, p = 0.612). Radiotherapy and chemotherapy were more frequently administered in the conventional white-light group (p = 0.0404 and p = 0.0085, respectively). Conclusions 5-ALA fluorescence-guided surgery significantly increases the rate of gross total resection in high-grade glioma patients but does not independently confer a survival advantage. Survival outcomes are primarily influenced by the extent of resection, adjuvant therapy, and functional status. Integration of 5-ALA within a comprehensive oncological framework may enhance its clinical utility. Full article
(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)
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