Prostate cancer (PCa) is the second most diagnosed cancer and the fifth leading cause of cancer death among men worldwide. Androgen receptor (AR), as a ligand-activated transcription factor, is important for both prostate development and PCa progression. Understanding the molecular mechanisms of prostate carcinogenesis has led to the development of therapeutic strategies targeting AR. Inhibiting AR is currently the gold standard for hormone therapy. However, eventually resistance to therapy occurs. The activation of AR by supraphysiological androgen levels (SAL) used currently in clinical trials paradoxically also inhibits PCa progression and induces cellular senescence. Interestingly, circadian rhythm controls hormone biosynthesis including androgens. Intriguingly, SNPs in several clock genes have been associated with PCa risk linking increased cancer risk with day-night shifts. Here, we discuss whether the efficacy of hormone therapeutics depends on the biological clock. It emerges that androgens control the expression of clock genes also intersecting with SAL-induced cellular senescence suggesting a complex and understudied network that governs PCa progression. This review highlights the multifaceted roles of AR signaling in PCa, emphasizing its ability to promote cellular senescence by AR-targeted therapy via genomic and non-genomic pathways and crosstalk with the regulation of circadian clock genes. The intricate interplay between circadian rhythm, androgen signaling, and cellular senescence presents a promising yet underexplored research area in PCa and suggests a multilayered regulatory network that could shape PCa progression and treatment outcomes. Unraveling this network may uncover novel chronotherapeutic strategies and provide new insights into disease, prognosis, and therapy options.

PTTG1 is an oncogene that is highly expressed in various cancers and is involved in regulating the cell cycle in neuroblastoma (NB) cells. However, the specific role of PTTG1 in NB has not been extensively reported. We undertook this study to investigate the expression of PTTG1 in various NB cell lines to identify the gene expression patterns.

Salivary gland lymphadenoma is an uncommon neoplasm and malignant transformation is even rarer. Reported tumor types include basal cell adenocarcinoma, sebaceous carcinoma, EBV-associated lymphoepithelial carcinoma, and undifferentiated carcinoma; a squamous phenotype has not been reported. Here we describe the case of a 62-year-old female who underwent total parotidectomy for a painful parotid gland mass of uncertain duration. On microscopic examination, a high grade lymphoepithelial carcinoma with squamous and poroid features arising in a non-sebaceous lymphadenoma was recognized. Both benign and malignant components expressed CK5/6 and ΔNp63 (p40), however SOX2 was overexpressed in the malignant component. S100, SOX10, CD117, PLAG1 and HMGA2 immunostains were negative. In-situ hybridization for high-risk HPV RNA and EBER were also negative. Fluorescence in situ hybridization revealed MAML2 rearrangement with RNASeq confirming a YAP1::MAML2 fusion product. This case highlights a novel salivary gland malignancy type arising from lymphadenoma, for which molecular testing was critical in establishing primary origin, and thus excluding the more common metastatic squamous cell carcinoma.

This study aimed to investigate the efficacy and safety of fruquintinib plus sintilimab in mismatch repair-proficient (pMMR)/microstatellite stable (MSS) refractory metastatic colorectal cancer (mCRC).

Accurate classification of genetic variants is critical for precision medicine, particularly hereditary diseases such as breast cancer. However, widely used tools like MutPred and Combined Annotation Dependent Depletion (CADD) offer genome-wide pathogenicity predictions that often overlook disease-specific variant behavior, limiting their clinical utility. This study addresses that gap by training and benchmarking nine machine learning (ML) models-including ensemble and baseline classifiers-on a breast cancer gene-specific dataset rich in conservation scores, functional annotations, and allele frequency features. Among all models, the Extra Trees model achieved the highest performance, with an accuracy of 0.999 and a 95% confidence interval of (0.998-1.000). recursive feature elimination identified the most informative genomic features, enhancing model efficiency. To ensure clinical transparency, we applied interpretability techniques including Local Interpretable Model-Agnostic Explanations and permutation feature importance, which highlighted the key drivers of each prediction. The calibration curve further confirmed the reliability of predicted probabilities, supporting their potential use in clinical decision-making. On an independent ClinGen dataset, Extra Trees achieved 99.1% accuracy and outperformed widely used predictors confirming its robustness and clinical applicability. This is the first comprehensive benchmarking study to apply ML models specifically to breast cancer-related missense variants using disease-gene-specific training data and integrated interpretability. Our results show that disease-specific ML approaches outperform general predictors, offering improved reliability, transparency, and relevance to clinical genomics. By bridging the gap between broad genome-wide tools and tailored clinical prediction, this study lays the foundation for implementing ML-driven pathogenicity prediction in breast cancer diagnostics and precision medicine, with potential expansion to other disease contexts.

Epithelioid fibrous histiocytoma (EFH) is a rare, benign cutaneous neoplasm, thought to be distinct from benign fibrous histiocytoma because of its characteristic anaplastic lymphoma kinase (ALK) gene rearrangements. This article presents 3 cases of EFH with unusual multinucleated giant cells, all located on acral sites. The patients, 2 women and 1 man, ranged from 24 to 63 years of age. Histopathologically, these cases exhibited well-circumscribed lesions in the dermis, composed of sheets of epithelioid cells with abundant eosinophilic cytoplasm and round nuclei within a fibrous stroma. Notably, numerous multinucleated giant cells were present, all showing ALK positivity. Clinical follow-up, ranging from 3 to 120 months, revealed no recurrence, reinforcing the benign nature of EFH. These findings highlight the importance of distinguishing EFH from other cutaneous epithelioid neoplasms with multinucleated giant cells. The presence of ALK rearrangement serves as a critical diagnostic marker. This case series expands the histopathologic spectrum of EFH and emphasizes the need for awareness of its diverse presentations to avoid misdiagnosis.

Clear cell renal cell carcinoma (ccRCC) is the most common renal tumor with a highly aggressive phenotype and poor prognosis. A key process in tumor progression is epithelial-mesenchymal transition (EMT), as a result of which cells acquire the ability to metastasize. An important inducer of the EMT process is inflammation. A negative regulator of inflammation is the Monocyte Chemoattractant Protein-1 Induced Protein 1 (MCPIP1), which by regulating the immune response may contribute to inhibiting tumor progression. A specific function of the MCPIP1 protein is RNase activity regulating the level of mRNA and miRNA expression. In our studies, we investigated how the MCPIP1 protein affects the EMT process, migratory activity and the level of tumor suppressor genes in clear cell renal cell carcinoma cell lines, tumor tissues of patients and an in vivo xenotransplantation model. We have shown that MCPIP1 regulates the EMT process by preventing cells from acquiring a mesenchymal phenotype. MCPIP1, due to its RNase activity, degrades miRNA-519a-3p, miRNA-519b-3p and miRNA-520c-3p, thereby actively affecting the levels of SFRP4, KREMEN1, ZNRF3, CXXC4 and CSNK1A1 inhibitors and inhibiting the Wnt pathway by inactivating β-catenin and, consequently, inhibiting the EMT process. Furthermore, MCPIP1 regulates the level of Rho proteins, phosphorylation of FAK and Src kinases, and consequently actin remodeling. The obtained results indicate that the lack of MCPIP1 RNase activity activates genes and processes associated with the migratory activity of cancer cells. In summary, the results obtained in this doctoral thesis indicated that MCPIP1 may regulate the progression of clear cell renal cancer at various levels of proangiogenic and prometastatic factors, as well as by influencing the EMT process.

An imbalance between the expression of cell cycle-promoting and cell cycle-inhibiting genes triggers uncontrolled cell cycle progression in cancer cells. However, the mechanism controlling the expression of cell cycle-related genes, especially those whose expression is mediated by RNA-binding proteins (RBPs), remains elusive.

Precision medicine has personalized anticancer therapies and has been considered standard practice. Although current cancer genomic profiling tests are powerful tools to predict the efficacy of molecular targeted drugs or immune checkpoint inhibitors, they are not readily applicable for classical anticancer agents. In this study, we report a novel concept of phenotype-based classification using machine learning analysis of gene expression patterns to predict the effectiveness of anticancer agents.

Human POLE and POLD1 genes encode DNA polymerases responsible for genome replication and proofreading of DNA synthesis errors. Germline and somatic POLE/POLD1 mutations compromising the polymerase fidelity cause cancers with high mutational burden. Ultramutation is associated with a better prognosis and immunotherapy response, highlighting the need to define tumour POLE/POLD1 status unambiguously. Prior studies assessed the functional significance of numerous POLE/POLD1 variants in experimental models. However, the data remain scattered and difficult to evaluate by non-specialists, limiting their utility for research and clinical applications. Through manual literature curation, we integrated data from functional studies of clinically relevant POLE and POLD1 variants into PolED, a publicly available database (https://poled-db.org). PolED compiles information on variant effects in biochemical assays, yeast, mammalian cells, and mouse tumour models along with supporting references. It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.

The association between single nucleotide polymorphisms (SNPs) and fracture risk has been established in various studies. Androgen-deprivation therapy (ADT) for prostate cancer, while extending survival, increases the risk of osteoporosis and bone fracture. This study aimed to assess the predictive value of polygenic risk scores (PRSs) on bone events among prostate cancer patients undergoing ADT.

The Oncotype DX Breast Recurrence Score test was designed for HR+, HER2- early breast cancer (eBC) to assist in the decision-making process for de-escalating adjuvant chemotherapy (CT). Its validity and utility have been demonstrated prospectively across multiple studies, though data on older patients remain limited.

An integrated model combining clinical variables, radiomic features, and deep learning was developed to predict EGFR mutation status in patients with lung adenocarcinoma based on pretreatment 18F-FDG PET/CT imaging.

In Barrett's oesophagus (BO), the precursor of oesophageal adenocarcinoma, the adult stratified squamous epithelium is replaced by a simple columnar phenotype. This has been considered metaplasia, i.e. the inappropriate conversion from one adult cell type to another. Alternatively, BO could represent reversion to an embryonic-fetal state when the early foregut is initially lined by simple columnar epithelium. Exploration of this hypothesis has been hampered by inadequate molecular details of human oesophageal development. Here, we adopted single-cell transcriptomic and epigenomic approaches to discover and de-code the cell types that constitute the initial primitive columnar, transitory and subsequently stratified lower oesophageal epithelium. Each stage comprises several previously undefined epithelial subpopulations. Importantly, early foregut columnar epithelial cells share core regulatory and gene expression programmes with BO. Among these, HNF4A is identified as a prominent transcriptional regulator that forms the core of a regulatory network in early foregut columnar cells. These regulatory networks are also central to programmes known to be reactivated in BO. Collectively, these data argue that the path to BO involves reactivation of pathways that define primitive embryonic and fetal epithelial cell states.

Parallels between cancer and developmental states are being increasingly recognised as important. In a new study, Baker et al. use single-nucleus transcriptomic and chromatin profiling to assess cell states and gene regulatory networks in the developing human oesophagus, and draw parallels with the pre-cancerous condition Barrett's metaplasia. We spoke to first author Syed Murtuza Baker and corresponding author Andy Sharrocks, Professor at The University of Manchester, UK, to find out more.

Approximately 83,000 new cases of bladder cancer (BC) in the United States and 23,000 in Japan are confirmed per year, and the number of new BC cases increases every year. While the prognosis for localized cancer is favorable, treatment options for metastatic cancer are limited, and the prognosis is extremely poor.

Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is used to diagnose and stage Non-Small Cell Lung Cancer (NSCLC), where the supernatant is discarded.

Esophageal cancer is one of the most devastating cancers of the gastrointestinal tract. We will compare the expression levels of fibrillin-1 (FBN1) and fibrillin-2 (FBN2), a family of extracellular matrix glycoproteins, in esophageal cancer with normal adjacent tumor tissue.

Oxidative stress and metabolic disorders significantly contribute to the development of polycystic ovarian syndrome (PCOS). Heme oxygenase-1 (HMOX1) plays a key role in the degradation of heme and the regulation of oxidative stress, ferroptosis, and glycolipid metabolism. This study explored the relationship between HMOX1 promoter T-413A single nucleotide polymorphism (SNP, rs2071746), (GT)n dinucleotide repeat variant (rs3074372), plasma HMOX1 levels, and the risk of PCOS in Chinese women.

Tyrosine is associated with alterations in the tricarboxylic acid cycle in lung cancer, and exploring tyrosine-related genes (TRGs) has the potential to contribute to the construction of new sensitive prognostic biomarkers for patients with lung adenocarcinoma (LUAD).