NUT carcinoma is a rare and highly aggressive malignancy characterized by the rearrangement of the NUTM1 gene. It typically arises in midline structures, including the respiratory tract. Due to its rarity and poor prognosis, early diagnosis and effective treatment remain challenging. This report presents two cases of NUT carcinoma occurring in the respiratory tract, additionally, a review of the literature is provided to enhance understanding of this disease. Both patients were young females, one tumor was located in the larynx and the other in the left main bronchus. Endoscopic forceps biopsy samples revealed tumor growth beneath the superficial mucosal epithelium, arranged in sheets, cords, or nests with extensive necrosis. The tumor cells were uniform in size, with eosinophilic cytoplasm, ill-defined borders, and round or oval nuclei showing hyperchromasia and a high nuclear-to-cytoplasmic ratio. One case showed focal areas with squamous differentiation. Immunohistochemically, tumor cells were positive for P40, P63, and NUT, and fluorescence in situ hybridization detected NUT gene rearrangement, confirming the diagnosis of NUT carcinoma. One patient experienced rapid disease progression despite receiving chemotherapy and died within five months. Another patient declined further treatment after diagnosis. NUT carcinoma is a rare and aggressive malignancy of the respiratory tract with a poor prognosis. Early diagnosis through molecular testing is crucial for appropriate management. However, diagnosis is often delayed until advanced stages, contributing to low survival rates. Increased awareness of this tumor among clinicians and pathologists may facilitate earlier detection and potentially improve patient outcomes.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumour associated with a poor prognosis. Recent studies have suggested that ribonucleotide reductase subunit M2 (RRM2) could promote tumour progression. This study aims to explore the expression, function and mechanism of RRM2 in ICC by regulating ferroptosis through the HIF-1α signalling pathway.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most commonly mutated oncogene in solid tumors, detected in up to 30% of lung adenocarcinomas. This study aimed to address gaps in the literature by analyzing KRAS mutations (KRASM) in a large Australian population.

Intramuscular myxoma (IM) is a benign tumor that harbors GNAS missense variants. Distinguishing IM from low-grade myxofibrosarcoma (LGMFS) is challenging due to similarities in imaging and histological features. While molecular analysis aids differentiation, the low number of tumor cells available for DNA extraction necessitates highly accurate detection methods for variant identification. The aim of this study was to delineate molecular characteristics using next-generation sequencing (NGS) and to propose an optimal screening method in a clinical setting to differentiate IM from LGMFS.

Ovarian cancer exhibits high molecular heterogeneity and metastatic potential, contributing to its status as a leading cause of gynecologic cancer mortality. Cell polarity is essential in tumorigenesis, yet the role of Crumbs family proteins (CRBs), key regulators of apical-basal polarity, in epithelial ovarian cancer (EOC) remains unclear. In this study, we analysed CRB expression profiles using TCGA and GEO datasets, and validated our findings through immunohistochemical staining of ovarian tumour tissue microarrays. Among CRBs, CRB2 was significantly overexpressed in EOC tissues and correlated with poor patient prognosis. Functional assays revealed that CRB2 enhances ovarian cancer cell proliferation, migration, and invasion, while suppressing apoptosis. Immunofluorescence staining of planar cell polarity markers demonstrated that CRB2 induces polarity alterations in EOC cells. Furthermore, Western blot analysis suggested that CRB2 may activate the Wnt/planar cell polarity (PCP) signalling pathway, contributing to tumour progression. These findings identify CRB2 as a key modulator of cell polarity and a potential driver of EOC aggressiveness. CRB2 may serve as a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Circulating tumor DNA (ctDNA) analysis has emerged as a pivotal minimally invasive tool for early detection, monitoring, and treatment stratification in cancer patients. However, the accuracy and reliability of ctDNA assays are profoundly influenced by preanalytical variables. This review discusses the impact of biological features (circadian rhythm, age, and sex), lifestyle factors (diet, smoking, and physical activity), as well as technical aspects such as hemolysis, leukocyte lysis, and delayed plasma separation on ctDNA integrity and concentration. Fluctuations in ctDNA levels driven by these factors highlight the need for clear guidelines regarding precollection timing, dietary restrictions, and sample processing. Furthermore, the adoption of harmonized protocols is essential to reduce variability and improve reproducibility across clinical and research settings.

Chondrosarcoma (CS) has a prognosis largely influenced by tumor grade. Although IDH mutations have been reported in CS, impact on patient`s survival remains controversial. This study aims to assess prognostic relevance of IDH mutations on disease-specific survival (DSS), metastasis-free survival (MFS), and local recurrence-free survival (RFS), in a large cohort of CS patients.

Ferroptosis, the most common programmed cell death process, and immune checkpoints play increasingly prominent roles in glioma. However, the effects of ferroptosis on immune checkpoints on glioma remain unclear. The intracellular ROS levels of ferroptotic glioma cells were observed via fluorescence microscopy. The extracellular Acetyl-HMGB1 content of ferroptotic glioma cells was detected via an ELISA kit. Transwell chambers (8.0 μm) were used to detect the invasion ability of ferroptotic glioma cells. The ability of ferroptotic glioma cells to proliferate was detected via the CCK-8 reagent. The apoptosis of ferroptotic glioma cells was detected via an Annexin V-FITC apoptosis kit. The transcriptional levels of four immune checkpoints (CD80, CD155, HMGB1, and galectin-9) in ferroptotic glioma cells were detected via RT-PCR. Ferroptosis in glioma cells promotes the release of acetyl-HMGB1 and autophagy is involved in this process. Inhibiting extracellular acetyl-HMGB1 while inducing ferroptosis promoted the invasion and proliferation of glioma cells and inhibited apoptosis. Ferroptosis downregulated the transcription of CD155 and galectin-9 in glioma cells, but inhibition of extracellular acetyl-HMGB1 reversed the effect of ferroptosis on the downregulation of galectin-9 transcription. In conclusion, ferroptosis downregulates galectin-9 transcription via extracellular acetyl-HMGB1, thereby inhibiting the biological behavior of glioma cells.

Tumor heterogeneity in breast cancer is well recognized, but research has largely focused on primary tumors, while metastatic lesions, particularly brain metastases (BM), remain understudied. With the rising incidence of BM in metastatic breast cancer (MBC) and their poor prognosis, a deeper understanding of the molecular mechanisms driving BM formation, progression, and immune evasion is crucial for developing better therapeutic strategies. We performed an integrated analysis of BM and matched primary breast tumors using immunohistochemistry, in-situ hybridization, tumor-infiltrating lymphocyte (TIL) quantification, and bulk RNA sequencing. Tumor receptor status, gene expression profiles, immune cell composition, and pathway alterations were analyzed in ten patients with paired samples. Changes in receptor status were observed between primary tumors and BM, including alterations in estrogen receptor and HER2 expression. RNA sequencing revealed differentially expressed genes and pathways, with an apparent downregulation of immune-related genes in BM. Immune profiling suggested a shift in the tumor microenvironment, with BM showing lower B- and CD8 + T-cell infiltration and a relative increase in M2 macrophages and follicular helper T-cells. While these findings are descriptive and limited by sample size, they point towards a potentially more immunosuppressive milieu in BM that may contribute to immune evasion and reduced responsiveness to checkpoint inhibitor therapy. Our study highlights molecular and immunological differences between primary breast tumors and BM. The altered immune landscape in BM, characterized by diminished TIL infiltration and an increase in immunosuppressive cells, warrants further investigation in larger, more homogeneous cohorts.

MRVI1 is a multifaceted gene whose functions in cancer vary across tissue types, acting either as a tumor-promoting or tumor-suppressive factor. In colorectal cancer, MRVI1 functions downstream of p53, and its loss enhances malignant phenotypes; however, the effects of MRVI1 overexpression have remained unclear. In this study, we established HCT116 colorectal cancer cells stably overexpressing MRVI1 to examine its functional impact. Western blot analysis confirmed robust expression of the V5-TurboID-MRVI1 fusion protein in the established cell line. Cell proliferation assays showed that MRVI1 overexpression markedly reduced cell growth compared with control cells under standard culture conditions. Trypan blue staining demonstrated that MRVI1 overexpression did not increase cell death, indicating that the reduction in cell number reflects a cytostatic rather than cytotoxic effect. These findings provide direct evidence that MRVI1 suppresses the proliferation of colorectal cancer cells when overexpressed. Combined with previous reports demonstrating that MRVI1 knockdown promotes proliferation and invasive behavior in colorectal cancer cells, our results support the view that MRVI1 contributes to p53-associated growth control in this tumor lineage. These observations further reinforce the concept that MRVI1 is a context-dependent, multifaceted cancer-associated gene.

Treatment selection for patients with polycythemia vera (PV) is based on patient age and history of thrombosis. The standard treatment is low-dose aspirin and phlebotomy, with cytoreductive therapy added for high-risk PV. Clinical trials in patients with PV have shown that ropeginterferon alfa-2b (ropeg-IFN) treatment is safe, efficacious, and reduces JAK2 V617F allele burden. As PV mainly affects individuals aged 60 years and older, incidence estimates have been increasing. Here we report 3 cases of elderly patients treated with ropeg-IFN who experienced no serious adverse events. All 3 patients achieved and maintained complete hematologic response with reduced JAK2 V617F allele burden. Ropeg-IFN is an effective and safe therapy for elderly patients with PV that also improves quality of life.

Ropeginterferon alfa-2b (ropeg-IFN), a treatment that allows for prolonged dosing intervals through site-specific PEGylation, has been approved for the treatment of polycythemia vera (PV) in patients for whom existing therapies are insufficient or unsuitable. In this case report, we describe a woman in her thirties who was treated with ropeg-IFN. Blood tests showed increased levels of all three blood cell lineages, and PV was diagnosed following bone marrow examination. The patient was enrolled in a clinical study in which she received ropeg-IFN because phlebotomy could not be performed due to difficulty with securing peripheral vascular access. Complete hematologic response (CHR) was achieved 12 weeks after the start of administration, and molecular response (MR) with a JAK2 V617F allele burden of <1% was achieved after approximately 156 weeks of continuous administration of ropeg-IFN. Alopecia (grade 1) occurred as an adverse event, but resolved after ropeg-IFN dose reduction. The patient maintained CHR and MR for 2 years following treatment discontinuation. We also discuss the potential benefit of ropeg-IFN in low-risk PV patients who were not previously considered candidates for aggressive cytoreductive therapy.

We report two cases of polycythemia vera (PV) treated with ropeginterferon alfa-2b (ropeg-IFN) in which hematologic control was maintained without therapy after treatment discontinuation. The patients achieved complete response (CR) at 14 and 22 weeks after treatment initiation, respectively. After discontinuation of ropeg-IFN, Patient 1 has maintained hematocrit (Ht) <45% for 3 years and 3 months, while patient 2 has maintained CR for 1 year and 5 months. Clinical trials have demonstrated that ropeg-IFN reduces the JAK2 V617F allele burden, which is recognized as an independent risk factor for disease progression and thrombosis, apart from traditional factors such as age and prior cardiovascular events. To improve the prognosis of PV, it is essential to accumulate clinical evidence on trends in JAK2 V617F allele burden and the conditions required to maintain hematologic control after discontinuation of ropeg-IFN therapy in real-world settings.

Cancer progression is governed by a dynamic interplay between genetic alterations and epigenetic modifications, which shape tumor adaptation, immune evasion, and therapy resistance. Among these modifications, epigenetic regulation of autophagy, a cellular process critical for maintaining homeostasis, has emerged as a key player in cancer biology. While autophagy suppresses tumor initiation by eliminating damaged organelles and reducing oxidative stress, tumors can hijack this process to sustain survival under metabolic stress and promote resistance to chemotherapy, radiotherapy, and immunotherapy. This review explores the intricate crosstalk between DNA methylation, histone modifications, and non-coding RNAs in controlling autophagy-related genes and their dual role in cancer progression. We also highlight the therapeutic potential of targeting epigenetic modulators (HDAC and DNMT inhibitors) and autophagy regulators to overcome multidrug resistance. Understanding the epigenetic-autophagy axis provides novel insights into cancer treatment, emphasizing the need for personalized approaches that balance autophagic activity to enhance therapy efficacy and improve patient outcomes. This emerging field presents a promising frontier for epigenetic-driven precision medicine in oncology.

The epigenetic landscape of cancer reveals how microRNAs (miRNAs) regulate gene expression through epigenetic mechanisms, alongside advancements in miRNA-based biosensor technology for early detection. Epigenetics, which studies heritable gene function changes without altering DNA sequences, has transformed our understanding of cancer by highlighting the complex interaction between genetics and environment. Key mechanisms such as DNA methylation, histone modification, and chromatin remodelling shape gene expression and cellular identity, with dysregulation in these processes often marking cancer development. Within this framework, miRNAs act as crucial epigenetic regulators, influencing gene expression post-transcriptionally and functioning as either oncogenes (oncomiRs) or tumour suppressors. miRNAs interact with epigenetic modifiers like histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), creating regulatory networks that affect cancer cell behaviours such as proliferation, differentiation, and apoptosis. To apply these molecular insights, the chapter reviews innovations in miRNA-targeting biosensors. Electrochemical and photoelectrochemical biosensors, enhanced with nanotechnology, are designed to detect miRNAs at ultra-low concentrations in biological fluids, addressing limitations of conventional cancer diagnostics. These biosensors offer high sensitivity, specificity, and point-of-care potential, with benefits such as rapid response, cost-efficiency, and miniaturization. Case studies showcase miRNA-based biosensors targeting cancer-related miRNAs, underscoring their promise in early cancer detection and monitoring. By bridging epigenetics, miRNA regulation, and biosensor technology, these emerging diagnostic tools offer new possibilities for improving cancer diagnosis and patient outcomes.

The dysregulation at the epigenetic level, such as DNA methylation, histone modifications, and changes in noncoding RNA, plays an important role in many serious human pathologies, including cancers. Epigenetics modulates the expression of tumor-related genes without any changes in the DNA sequences, thus understanding the epigenetic profile is a promising way to clarify the underlying mechanism of cancers as well as other diseases. Specific techniques like chromatin immunoprecipitation followed by sequencing (ChIP-seq), whole-genome bisulfite sequencing (WGBS), or mass spectrometry (MS) were developed to obtain epigenetic data. This leads to the need for robust tools to analyze and interpret these high-throughput data. With the development of bioinformatics tools, several complex interactions between DNA methylation and chromatin modification were clarified to help researchers control gene expression. Moreover, data science, and information technology, especially machine learning and deep learning, have revolutionized the study of epigenetics in cancer, providing powerful tools to integrate both genetic and epigenetic data, as well as clinical/para-clinical characteristics to enhance the accuracy of cancer diagnosis and treatment strategies. In this study, we will provide an overview of epigenetics' role in cancer, and more importantly, an update on the application of bioinformatics and data science in the epigenetic field for cancers. Integrating epigenetic data with other data like omics and clinical data with the help of bioinformatics and data science is an emerging direction for deciphering the epigenetic landscape of cancer and identifying potential therapeutic targets.

One of the three most common cancers in the world today is breast cancer. In recent years, molecular biology studies have highlighted the role of gene mutations. Epigenetic modifications have also been studied and have been shown to be one of the main contributors to the development and progression of breast cancer. Targeting these epigenetic regulatory mechanisms is considered a potential therapeutic strategy with the goal of inhibiting tumor progression and restoring normal gene activity. Epigenetic research has shed light on the important role of epigenetics in various aspects of breast cancer development, the underlying mechanisms of breast cancer, and its potential applications in improving diagnosis, prognosis, and treatment. These findings highlight the transformative potential of epigenetics in advancing the understanding and management of breast cancer. From there, it opens opportunities to detect breast cancer early even in a non-invasive way.

Ovarian cancer is a highly heterogeneous and lethal gynecological malignancy, with its progression tightly regulated by both genetic and epigenetic mechanisms. Among the epigenetic regulators, histone modifications-including acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation-have emerged as pivotal modulators of chromatin architecture and gene transcription. These post-translational modifications, governed by specific histone-modifying enzymes, shape the transcriptional landscape of tumor cells and influence key oncogenic processes such as cellular proliferation, invasion, stemness, DNA repair, and chemotherapy resistance. Dysregulation of enzymes such as histone acetyltransferases (HATs), deacetylases (HDACs), methyltransferases (HMTs), demethylases (HDMs), ubiquitin ligases, and SUMO ligases has been implicated in the pathogenesis of ovarian cancer and is associated with adverse clinical outcomes. Importantly, these modifications are reversible, rendering them tractable therapeutic targets. This review provides a comprehensive synthesis of the major classes of histone modifications and their biological functions in ovarian cancer, highlights recent insights into the interplay between different modifications (crosstalk), and evaluates ongoing therapeutic strategies that aim to reverse epigenetic dysregulation. By elucidating the complex epigenetic landscape, this review supports the development of next-generation diagnostic, prognostic, and therapeutic approaches in ovarian cancer.

Malignant melanoma is the most aggressive and lethal type of skin cancer associated with increased mortality rates. Moreover, beyond the genetic background, the altered epigenetic landscape (e.g., abnormal patterns of DNA methylation, aberrant histone modifications and de-regulated expression levels of ncRNAs) further contributes to the pathophysiology of the disease. In addition, despite the improvement of current anti-melanoma strategies and the development of new therapeutic approaches, the 5-year survival among melanoma patients is still high, mainly due to acquired-drug resistance. On the other hand, phytochemicals have been associated with various health-promoting properties through pleiotropic mechanisms including acting as potent epigenetic regulators restoring back a normal phenotype in various experimental cancer models. In this review article, we discuss the general characteristics of malignant melanoma and current therapeutic approaches while we report the epigenetic basis of the disease along with the main compounds capable of restoring a normal epigenetic landscape. Finally, we describe the role of various phytochemicals in targeting the epigenome of malignant melanoma thereby potentially acting as an alternative therapeutic approach.