UDP-Gal-β-1,4 galactosyltransferase-V (GalT-V) is a member of a large family of galactosyltransferases whose function is to transfer galactose from the nucleotide sugar UDP-galactose to a glycosphingolipid glucosylceramide, to generate lactosylceramide (LacCer). It also causes the N and O glycosylation of proteins in the Trans Golgi area. LacCer is a bioactive lipid second messenger that activates an "oxidative stress pathway", leading to critical phenotypes, e.g., cell proliferation, migration angiogenesis, autophagy, and apoptosis. It also activates an "inflammatory pathway" that contributes to the progression of disease pathology. β-1,4-GalT-V gene expression is regulated by the binding of the transcription factor Sp-1, one of the most O-GlcNAcylated nuclear factors. This review elaborates the role of the Sp-1/GalT-V axis in disease phenotypes and therapeutic approaches targeting not only Sp-1 but also Notch-1, Wnt-1 frizzled, hedgehog, and β-catenin. Recent evidence suggests that β-1,4GalT-V may glycosylate Notch-1 and, thus, regulate a VEGF-independent angiogenic pathway, promoting glioma-like stem cell differentiation into endothelial cells, thus contributing to angiogenesis. These findings have significant implications for cancer and cardiovascular disease, as tumor vascularization often resumes aggressively following anti-VEGF therapy. Moreover, LacCer can induce angiogenesis independent of VEGF and its level are reported to be high in tumor tissues. Thus, targeting both VEGF-dependent and VEGF-independent pathways may offer novel therapeutic strategies. This review also presents an up-to-date therapeutic approach targeting the β-1,4-GalT-V interactome. In summary, the β-1,4-GalT-V interactome orchestrates a broad network of signaling pathways essential for maintaining cellular homeostasis. Conversely, its dysregulation can promote unchecked proliferation, angiogenesis, and inflammation, contributing to the initiation and progression of multiple diseases. Environmental factors and smoking can influence β-1,4-GalT-V expression and its interactome, whereas elevated β-1,4-GalT-V expression may serve as a diagnostic biomarker of colorectal cancer, inflammation-exacerbated by factors that may worsen pre-existing cancer malignancies, such as smoking and a Western diet-and atherosclerosis, amplifying disease progression. Increased β-1,4-GalT-V expression is frequently associated with tumor aggressiveness and chronic inflammation, underscoring its potential as both a biomarker and therapeutic target in colorectal and other β-1,4-GalT-V-driven cancers, as well as in cardiovascular and inflammatory diseases.

Artificial intelligence (AI) and its machine learning and deep learning algorithms have shown promise in oncological practice. Spatial information analysis in the context of cancer is crucial for its diagnosis and treatment because it can provide an understanding of tumor-microenvironment interactions and reveal insights into response to treatment. AI tools can analyze spatial information at multiple scales, highlighting key disease, clinical, and genetic phenotypes that may reveal underlying mechanisms and molecular markers of response and resistance within the tumor and its microenvironment. By examining tumor interactions at macroscopic (diagnostic imaging) and microscopic (pathology slides and spatial biology) levels, AI can assist in making important diagnostic and prognostic decisions. In this review, we first present an overview of AI and the need for multiscale spatial information in oncology. Then, we examine growing AI applications in the analysis of such information, focusing on diagnostic imaging, digital pathology, and spatial molecular biology. We also discuss applications of large-scale foundation models and task-oriented agentic AI in these fields as emergent technologies. Then, we discuss current limitations for the clinical translation of AI into regular utilization in cancer care and discovery.

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.

Colorectal cancer (CRC) is not only the third most common cancer worldwide, with 1.1 million new cases per year; it is also the second leading cause of cancer death. However, mortality has decreased since 2012 due to early detection programs and better therapeutic approaches. While many patients are diagnosed at an early stage, there is up to 50% relapse after optimal initial treatment. Therefore, it is crucial to explore the mechanism underlying the development of recurrences and metastasis. It is known that tumors release dormant cells that escape chemotherapy and nest in a target organ without proliferating. Under certain circumstances that are not yet entirely clear, they can be activated and metastasize. Therefore, the objective of this work is to explore the detailed mechanisms of dormancy, including early detection of recurrence and therapeutic approaches for the treatment of CRC. The specific objectives are to determine biomarkers that may be useful in identifying dormant cells to detect minimal residual disease (MRD) after surgery and predicting disease progression, as well as evaluating biomarkers that are susceptible to therapeutic intervention.

Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.

Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.

This Special Article provides a comprehensive review and expert commentary on the prospective clinical implementation of artificial intelligence (AI) in the detection of prostate cancer from digital prostate biopsies, as presented in the original research by Flach et al. It contextualizes the study within broader developments in digital pathology and AI, addressing barriers to adoption and the implications for diagnostic workflows and pathology practice.

The discovery of a class of long noncoding RNAs (lncRNAs), including lncRNAs of the small nucleolar RNA (snoRNA) host gene family, SNHG, has led to growing interest in the study of both snoRNAs themselves and the genes encoding them. Currently, of the 232 known snoRNA genes, only 32 have been confirmed to have lncRNAs. At the same time, a positive correlation has been shown between the expression of lncRNAs and snoRNAs encoded by a common host gene of the SNHG family. Thus, lncRNA of the SNHG1 gene correlates with snoRNAs SNORD22 and SNORD25-31, and lncRNA of the SNHG16 gene, with snoRNAs SNORD1A, SNORD1B, and SNORD1C. There is evidence that SNHG lncRNAs can participate in oncogenesis both through regulatory functions inherent to lncRNAs and by influencing ribosome biogenesis. At the same time, information has accumulated on the "extraribosomal" functions of snoRNAs. In addition to a brief excursion into the biological functions of snoRNAs and SNHG lncRNAs, we present a comprehensive review of data on the role of these two types of noncoding RNAs in the pathogenesis of ovarian cancer, the most insidious cancer of the female reproductive system. The influence of these regulatory RNAs on the main processes of ovarian oncogenesis, such as apoptosis, epithelial-mesenchymal transition, cell cycle control, and DNA methylation mechanisms in this type of cancer is considered. The prospects for clinical application of regulatory RNAs due to their influence on the level of drug resistance are also discussed.

The main functional parts of the glymphatic system are perivascular spaces and surrounding astrocytes. Cerebrospinal fluid enters the brain parenchyma from subarachnoid cisterns through perivascular Virchow-Robin spaces and passes into the interstitium through aquaporin channels in astrocytes. Then, cerebrospinal fluid removes metabolic products and mixes with interstitial fluid. Outflow of cerebrospinal fluid with metabolic products from the brain parenchyma occurs in three ways. The first route is periarterial through intermuscular spaces in the middle layer of cerebral arteries. The second route is perivenous. The third route is lymphatic through meningeal or sinus-associated lymphatic vessels. They provide drainage of macromolecules and immunocompetent cells from the brain to the cervical lymph nodes. Gliomas are accompanied by inhibition of normal cerebrospinal fluid outflow pathways, mainly due to additional intracranial tissue, and compensatory cerebrospinal fluid outflow along the spinal cord. Reduced cerebrospinal fluid release with impaired outflow contribute to accumulation of toxic metabolic products, proinflammatory cytokines and chemokines. Transport of antigens to lymph nodes is inhibited that disrupts antitumor immunity. Impaired cerebrospinal fluid circulation also reduces the effectiveness of intracranial drug delivery. One of the mechanisms of pathogenesis of glioma metastasis is based on migration of tumor cells along classical and meningeal lymphatic pathways. Damage to the latter contributes to metastasis.

The majority of meningiomas - benign tumors with an extremely low metastasis tendency. Only singular observations of extracranial metastasis of WHO Grade I benign meningiomas are described in the literature. Despite the intensive study of meningiomas' molecular biology, there are currently no reliable markers indicating the possibility of their metastasis.

Surgery of meningiomas of the craniocervical region is one of the most difficult parts of neurosurgery due to the closeness of the brainstem, caudal group of the cranial nerves (CNs) and vertebral artery. According to the literature, suffering of the caudal group of CNs is between 20 and 55% according to different authors. In their dysfunction, the recovery of CNs is long-term and requires joint efforts by both the medical team and the patient and his family.

Malignant transformation of fibrous dysplasia in McCune-Albright syndrome is observed in less than 1% of cases, thus osteosarcoma is developing more frequently. According to the search in the PubMed database over the last 5 years, 13 publications were found, but none of them described cerebral cranium damage.

Recent studies have revealed that the tumor microenvironment (TME) mediates neutrophil activation through multicomponent collaborative regulatory mechanisms, serving as a key driver of NETs formation. Cytokines, platelets, and complements activate neutrophil signaling pathways, ultimately forming NETs with protumorigenic properties in the TME. Notably, exogenous stimuli such as surgery, chronic stress, and pathogens can regulate NETs formation by remodeling the TME. However, the regulatory factors that induce NETs formation have not yet been systematically elucidated. Despite the identification of several factors that initiate the formation of NETs, the potential involvement of additional mechanisms remains inadequately understood. There is an urgent need for thorough mechanistic investigations utilizing cell lines and animal models in cancer. These studies will yield essential insights necessary for the formulation of targeted therapeutic approaches. This review delves into the mechanisms behind neutrophil extracellular traps (NETs) formation, tumor microenvironmental regulation of NETs formation, and exogenous stimuli that mediate tumor biological behaviors by inducing NETs. Gaining insight into these mechanisms will enhance our understanding of NETs and aid in crafting more precise strategies to inhibit tumor progression.

Phosphatidylcholine (PC), a core component of eukaryotic cell membranes essential for maintaining membrane integrity, has emerged as a critical regulator in oncogenic metabolic reprogramming. Accumulating evidence reveals that dysregulated PC metabolism constitutes a central mechanism driving malignant tumor progression. This review systematically delineates the biosynthetic pathways (Kennedy pathway, PEMT pathway, Lands cycle) and catabolic processes (phospholipase-mediated hydrolysis via PLA2, PC-PLC, and PLD) governing PC homeostasis. We highlight how PC metabolic networks orchestrate pro-tumorigenic effects via multifaceted mechanisms, such as enhancing membrane biosynthesis to support rapid tumor proliferation, activating some proliferative signaling cascades coupled with apoptosis suppression, remodeling the immunosuppressive microenvironment, et al. Notably, small-molecule inhibitors targeting key PC metabolic enzymes (e.g., RSM-932A, FIPI) demonstrate promising anti-tumor efficacy in preclinical models, though therapeutic outcomes are constrained by metabolic plasticity and tumor heterogeneity. By integrating recent advances in lipidomics and spatial metabolomics, this synthesis not only deciphers the evolutionary logic underlying PC-driven oncogenesis but also proposes innovative therapeutic strategies combining metabolic inhibitors with immune checkpoint modulators. Our analysis provides a conceptual framework for targeting phospholipid vulnerabilities in cancer, paving the way for precision oncology applications.

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often late diagnosis of this aggressive entity. We present a case of a 71-year-old male patient diagnosed with metastatic pancreatic carcinosarcoma who received four lines of palliative-intent treatment: gemcitabine and nab-paclitaxel, modified FOLFIRINOX, GTX, and doxorubicin. With careful selection of chemotherapeutic regimen as well as his ability to tolerate four lines of treatment, this resulted in an unprecedented 26-month survival. We also reviewed the literature on the histopathology, diagnosis, and treatment of this rare entity.

Since cancer is often linked to the aging process, the importance of cellular senescence in cancer has come under the spotlight. While senescence in cancer cells can serve as a natural barrier against cancer due to its proliferation arrest, its secretory phenotypes and alterations in the surface proteome can paradoxically promote or suppress tumor progression. Senescent cancer-associated fibroblasts, endothelial cells, and immune cells can also contribute to cancer promotion. During therapeutic interventions for cancer, not only their therapeutic effects, but also therapy-induced senescence may have an impact on cancer outcomes. Senotherapeutics, therapy targeting senescent cells, have been reported as novel cancer therapy in recent studies, and the combination of senescence induction and senotherapeutics has been increasingly recognized. Although some clinical trials of senotherapeutic drugs for cancer with or without senescence-inducible therapy are ongoing, there is as yet no satisfactory clinical application. With further research into targeting senescence in oncology, it is expected that senotherapeutics, particularly in combination with senescence-inducing therapy, will become a novel therapeutic strategy.

This study investigates two cases of stage IVb de novo multi-metastatic nasopharyngeal carcinoma (NPC) that responded to immunotherapy but resulted in different outcomes. Case 1 involved a multi-metastatic NPC patient (T4N3M1) with extensive bone and lymphatic metastases and severely impaired physical condition (ECOG PS 2) who showed significant tumor reduction after one cycle of immunotherapy combined with non-platinum chemotherapy, with no radiation exposure. Due to financial difficulties, the patient received intermittent immunotherapy plus chemotherapy and survived 28 months with a good quality of life. Case 2 describes a multi-metastatic NPC patient (T3N2M1) with multi-organ (bone and liver) metastases and good performance status (ECOG PS 0) who underwent standard chemotherapy, immunotherapy, and radiotherapy but experienced rapid progression and died after 21 months. Immunotherapy combined with chemotherapy remains the standard for multi-metastatic NPC patients. Patients responsive to induction chemotherapy gain survival benefits from subsequent radiotherapy. However, the advantages and disadvantages of radiotherapy for immunotherapy-sensitive multi-metastatic NPC patients are still unclear. Radiotherapy (RT) can enhance local control and promote tumor antigen release, thereby complementing immunotherapy; yet it can also damage immune cells, leading to exhaustion and resistance. Therefore, balancing RT and chemotherapy is vital for optimizing immune synergy and preventing immune exhaustion.

Pulmonary carcinoids (PCs) are rare neoplasms involving typical and atypical carcinoids (TCs and ACs), defined histologically by absent or focal necrosis and mitotic counts (<2/mm2 vs. 2-10/mm2), respectively. Although uncommon overall, TCs and ACs represent the most frequent non-hematologic malignancies in the pediatric population. However, significantly less is known about PC in AYAs, a population often overlooked or analyzed within pediatric or adult cohorts. In this critical review, we analyzed existing literature on PCs in the AYA population using a question-and-answer format, emphasizing the substantial gap in current knowledge in this field and the urgent unmet clinical need for future scientific proposals. First, we analyzed epidemiology and the data availability about the association between PCs in AYA patients and genetic syndromes that typically reach the maximal diagnostic incidence within this age group. We then reviewed the available literature about the pathologic characteristics, clinical presentation, and treatment strategies for localized and metastatic disease in PC AYA patients. According to our findings, a significant lack of age-specific evidence and the need for international collaboration and prospective, AYA-focused clinical studies were underscored. Advancing research in this area is essential to improve understanding and develop tailored, evidence-based therapeutic approaches for this peculiar population.

Ferroptosis suppressor protein 1 (FSP1) has emerged as a critical regulator of ferroptosis, an iron-dependent form of programmed cell death with significant therapeutic potential in cancer treatment. Despite rapidly expanding research, current knowledge on FSP1 remains fragmented across various tumor types and experimental contexts. The aim of this review is to systematically integrate the latest evidence regarding the molecular structure, biological functions, and regulatory mechanisms controlling FSP1 expression, emphasizing its involvement in tumor progression and resistance to therapy. Readers can expect comprehensive coverage of FSP1's structural characteristics, enzymatic roles, transcriptional and post-transcriptional regulation, and its pathological significance in hepatocellular carcinoma, colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, and leukemia. We further evaluate emerging therapeutic strategies targeting FSP1 aimed at overcoming resistance and improving clinical outcomes. Relevant studies were systematically identified by searching PubMed, Web of Science, and Embase databases, focusing particularly on the recent and impactful literature to guide future research directions.