Fibrotic interstitial lung diseases (F-ILDs) are increasingly complicated by early-stage non-small cell lung cancer. For many of these patients, stereotactic ablative body radiotherapy (SABR) is the only feasible curative-intent option. However, pre-existing fibrosis markedly increases the risk of severe, sometimes fatal, post-treatment respiratory events. These episodes are usually labelled radiation pneumonitis (RP), yet their timing, distribution and lethality often resemble acute exacerbations (AEs) of the underlying interstitial lung disease (ILD) rather than classical, field-confined RP. In this narrative review, we synthesise observational data from the SABR series enriched for ILD, focusing on acute respiratory deterioration within weeks to months after treatment. We examine how inconsistent terminology and heterogeneous case definitions obscure the distinction between RP and radiation-triggered AE (RT-AE)-ILD, and we summarise clinical, radiological, physiological, dosimetric and biomarker risk factors. Mechanistic models suggest that radiation may amplify a primed fibrotic lung via convergent epithelial, endothelial and immune pathways, with potential modulation by antifibrotic therapy, corticosteroid exposure and infection. We argue that in patients with progressive F-ILD, at least a subset of post-SABR 'pneumonitis' episodes are better conceptualised as RT-AE, with implications for corticosteroid stewardship, infection prophylaxis and continuation of antifibrotics. Given the absence of trial-level evidence and the high baseline mortality of F-ILD, management must prioritise multidisciplinary evaluation, explicit shared decision-making and cautious individualisation rather than reflexive transplantation of RP algorithms. Prospective registries, standardised ILD phenotyping and translational studies are urgently needed to define risk boundaries and test whether antifibrotic-radiation strategies or particle therapies can safely deliver curative-intent treatment to this highly vulnerable population.

Physical performance strongly influences peri-treatment outcomes in gastric cancer (GC), yet simple molecular markers reflecting functional status are lacking. Lipidomics may help identify circulating biomarkers linked to physical fitness.

To assess whether physical performance is associated with distinct plasma lipidomic profiles in GC patients.

Nineteen male GC patients (60-75 years) from the PROTECT trial were classified as high- (HighP) or low-performance (LowP) based on the 6-min walk test. Plasma lipidomics (LC-MS/MS) quantified 232 lipid species and a total of 25 fatty acids were quantified by gas chromatography-MS. Multivariate and univariate analyses, group comparisons, and correlations examined associations with clinical, anthropometric, and fitness parameters.

Lipid profiles differed by performance status. HighP patients showed higher phosphatidylinositol (PI 36:2) and trends toward increased plasmalogen phosphatidylethanolamines (PE), whereas sphingomyelin (SM 43:2) was higher in LowP patients. Plasmenyl-PE species correlated positively with functional tests, muscle mass, body mass index, and nutritional status; SM 43:2 correlated negatively. Acylcarnitines showed minimal associations.

GC patients with different physical performance status display distinct circulating lipid signatures. PI 36:2, PE plasmalogens, and SM 43:2 species appear linked to physical fitness, suggesting potential value as preoperative biomarkers. Validation in larger cohorts is warranted.

Cancer is a major global issue threatening the whole world, especially developing countries. Treatment of cancer using chemotherapy and radiotherapy has several consequences that negatively affect the quality of life of cancer patients.

Bee products have numerous pharmacological effects and clinical impacts due to their extraordinary chemical composition. The objective of the current work is to shed light on preclinical studies and clinical trials of bee products, particularly propolis, honey, and royal jelly, with special emphasis on their role in reducing the complications of chemotherapy and radiotherapy by employing a variety of databases. The search used specific keywords, including "bee products", "propolis", "honey", "royal jelly", "cancer", "clinical trials", "radiotherapy", and "chemotherapy". Only peer-reviewed randomized controlled trials (RCTs) and published research papers were included.

According to the literature review, bee-generated propolis, honey, and royal jelly have been used in animal models to reduce the adverse effects of radiotherapy and chemotherapy. Depending on the kind of cancer, different dosages and treatment times were used for certain bee products. Bee products are used in various forms, such as crude, in capsules, mouthwashes, tablets, and oils. Propolis, royal jelly, and honey are used at dosages up to 400 mg, 1 g, and 50 g, respectively. Clinical trials have further confirmed their efficacy in cancer treatment, either as standalone therapies or as supplements to conventional treatments.

It is crucial to investigate the active mechanisms of these products further and to include them in additional clinical trials as potential cancer treatments.

Lipid peroxidation triggers ferroptosis, a type of regulated cell death that is iron-dependent. Owing to its important role in tumor suppression, ferroptosis represents an extremely promising therapeutic target for cancer. QD394, a quinazolinone-based compound, was recently identified as a novel redox regulator with demonstrated cytotoxic and proapoptotic effects in pancreatic and breast cancer models. Preliminary RNA sequencing analysis suggested potential associations between QD394 treatment and ferroptosis, mitogen-activated protein kinase (MAPK) signaling, and angiogenic pathways. Cell Counting Kit-8 (CCK-8), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assays, as well as annexin V/PI staining, revealed that QD394 inhibited cell proliferation and induced apoptosis. Microtubule assembly, chick chorioallantoic membrane (CAM), and scratch assays demonstrated that QD394 suppressed angiogenesis. Notably, QD394-treated colorectal cancer (CRC) cells exhibited decreased levels of glutathione (GSH), solute carrier family 7 member 11 (xCT), and glutathione peroxidase 4 (GPX4), and increased levels of malondialdehyde (MDA) and lipid reactive oxygen species (ROS), suggesting that QD394 induces ferroptosis. Mechanistically, QD394 treatment reduced specific protein 1 (SP1) levels through ubiquitin-mediated proteolysis. Notably, overexpression of SP1 counteracted QD394-induced ferroptosis. Moreover, QD394 treatment significantly increased the ratio of p-JNK to total JNK in CRC cells, whereas SP1 overexpression effectively reversed this effect. In a xenograft model, QD394 significantly inhibited tumor growth and decreased tumor weight, and the expression of Ki-67, GPX4, and SP1. In contrast, 4-hydroxynonenal (4-HNE) and p-JNK levels were markedly elevated. Collectively, our findings reveal that QD394 triggers ferroptosis in CRC through the SP1/JNK signaling axis, highlighting its potential as a novel anticancer agent.

Antibody-drug conjugates (ADCs) have evolved in the last decade or two from carrying a single chemotherapy payload to carrying highly potent tubulin inhibitors and DNA damaging agents. While the latter have shown success in the clinic, efficacy has been constrained by therapeutic resistance, limited tumor penetration, and suboptimal immune activation. Currently, the ADC development space also includes the development of tumor-targeting monoclonal antibodies that carry dual-payloads, incorporating both cytotoxic agents and, for example, immunostimulatory molecules that could synergize direct tumor cell killing with reprogramming of the tumor immune microenvironment (TME). The translational and clinical pharmacology development strategy for ADCs is complicated by the need to understand the mechanism of action (MoA), the pharmacokinetics, and the pharmacodynamics of the different components of the ADC, and this gets even more complicated when two payloads are in play. The challenge lies, for instance, in understanding the MoA of each payload and the resulting synergy in effect, the increased number of analytes for bioanalysis, and the potential for added anti-drug antibody (ADA) formation due to more available epitopes in the ADC that could be recognized by the immune system. To date, no dual-payload ADCs have been approved, and this review is therefore intended to provide an overview on the translational science and clinical pharmacology strategies in the development of ADCs with two or more payloads based on what is currently known and published about single-payload ADCs and the authors' perspective.

Minimizing the transfusion burden is one of the primary clinical goals for most patients with myelodysplastic syndromes (MDS), which are incurable hematopoietic stem cell neoplasms. In some patients, supportive red blood cell transfusions can lead to clinical improvement, but frequent transfusions induce iron overload, which can have detrimental effects on cardiac and hepatic function, affect patients' quality of life, and incur additional healthcare costs. In this review, we summarize how erythropoiesis is regulated under steady-state conditions, dissect the molecular mechanisms underlying anemia in MDS, and review therapeutic approaches to overcome ineffective erythropoiesis in patients with these diseases.

A better understanding of the biological mechanisms underlying anemia in MDS is needed to develop targeted therapies for a personalized treatment approach. Anemia, a hallmark of MDS, highly affects patients' quality of life and contributes to overall morbidity. Current knowledge of the mechanisms of action of the available drugs targeting anemia in MDS is limited.

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide. The tumor microenvironment (TME) plays a pivotal role in LUAD progression, but the specific molecular mechanisms driving malignancy and immune evasion remain incompletely understood. Bone marrow stromal cell antigen 2 (BST2) has been implicated in other cancers, yet its functional role and therapeutic potential in LUAD require further elucidation.

We integrated single-cell RNA sequencing (scRNA-seq) data from primary LUAD tissues and normal lung tissues with bulk RNA-seq data from The Cancer Genome Atlas (TCGA)-LUAD and GEO cohorts. Malignant epithelial cells were identified using inferCNV analysis. Cellular trajectory and cell-cell communication analyses were systematically performed to delineate the malignant transformation process and its interactions with the TME. High-dimensional weighted gene coexpression network analysis further identified key functional modules within malignant subpopulations. The oncogenic role of BST2 was comprehensively validated through differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and in vitro cellular assays, including RT‑qPCR, MTT, colony formation, Transwell invasion, and wound healing experiments. In addition, we employed the tumor immune dysfunction and exclusion (TIDE) algorithm to evaluate its association with immunotherapy response and performed drug screening via the Clue.io platform to explore its therapeutic potential.

scRNA-seq analysis revealed significant heterogeneity in the TME and identified two distinct subpopulations of malignant epithelial cells. Trajectory analysis uncovered a specific lineage (Lineage 4) driving the normal-to-malignant transition, while cell communication analysis highlighted interactions between malignant cells and tumor-associated macrophages (TAMs) mediated by MIF and APP signaling pathways. High-dimensional weighted gene coexpression network analysis (hdWGCNA) identified a coexpression gene module (Module 1) specifically enriched in malignant subpopulations. By intersecting with a set of immunoregulatory genes, BST2 was ultimately determined as a key candidate oncogene. BST2 was significantly upregulated in malignant epithelial cells and TAMs, and its high expression was closely associated with poor patient prognosis. GSEA demonstrated that high BST2 expression was linked to the activation of crucial oncogenic pathways, including oxidative phosphorylation, Kras signaling, and epithelial-mesenchymal transition (EMT). In vitro validation further confirmed that BST2 knockdown suppressed LUAD cell proliferation, migration, and invasion. Furthermore, elevated BST2 expression was associated with reduced efficacy of immune checkpoint blockade (ICB) therapy.

Our study unveils BST2 as a critical oncogene in LUAD, promoting tumor progression and influencing the TME, particularly via TAM recruitment. BST2 expression predicts patient prognosis and immunotherapy response, positioning it as a promising biomarker and therapeutic target.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon biliary tumor with recognized malignant potential and a broad clinicopathological spectrum. Its diagnosis remains challenging, particularly in extrahepatic disease, due to limitations of cross-sectional imaging. We report a consecutive series of five patients diagnosed with IPNB in a tertiary hepatobiliary center, highlighting their clinical, radiologic, endoscopic, and pathological features. Most patients presented with obstructive jaundice or cholangitis, and lesions were predominantly located in the distal bile duct. Cross-sectional imaging showed bile duct dilatation but often yielded inconclusive findings or underestimated intraductal disease, frequently leading to suspicion of cholangiocarcinoma or indeterminate strictures. Cholangioscopy provided additional diagnostic value by enabling direct visualization of characteristic villous or papillary lesions and facilitating targeted biopsies, contributing variably to diagnostic clarification. Histopathology demonstrated high-grade dysplasia in most cases, with one patient harboring invasive carcinoma. All patients required biliary drainage, and most underwent or were considered for surgical resection. These findings highlight the diagnostic discordance between preoperative assessment and definitive pathological diagnosis in IPNB and underscore the limitations of conventional imaging. Cholangioscopy represents a valuable complementary tool in the evaluation of indeterminate biliary strictures, although its findings should be interpreted within a multimodal diagnostic approach.

It is now recognized that mitochondria play a crucial role in tumorigenesis; however, it has become clear that tumor metabolism varies significantly between cancer types. The failure of recent clinical trials aimed at directly targeting tumor respiration through oxidative phosphorylation inhibitors underscores the critical need for further studies providing an in-depth evaluation of mitochondrial bioenergetics. Accordingly, we comprehensively assessed the bulk tumor and mitochondrial metabolic phenotype in murine HER2-driven mammary cancer tumors and benign mammary tissue. Transcriptomic and proteomic profiling revealed a broad downregulation of mitochondrial genes/proteins in tumors, including OXPHOS subunits comprising Complexes I-IV. Despite reductions in tumor mitochondrial proteins, mitochondrial respiration was several-fold higher compared to benign mammary tissue, which persisted regardless of normalization method (wet weight, total protein content, and when corrected for mitochondrial content). This upregulated respiratory capacity could not be explained by OXPHOS uncoupling, suggesting HER2 signaling regulates intrinsic mitochondrial bioenergetics. In further support, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, attenuated mitochondrial respiration in NF639 murine mammary tumor epithelial cells. Together, this data highlights that the typical correlation between mitochondrial content and respiratory capacity may not apply to all tumor types and implicates HER2-linked activation of mitochondrial respiration supporting tumorigenesis in this model.

Over the past decade, clonal hematopoiesis (CH) has gained substantial attention as a prevalent, age-associated phenomenon with major implications for hematologic malignancy, cardiovascular disease, and mortality. CH arises from the clonal expansion of hematopoietic stem cells and progenitor cells harboring somatic mutations, most commonly in genes implicated in leukemia. Beyond chronological aging, CH evolution is shaped by lifelong exposure to inflammatory, metabolic, and environmental stressors, such as smoking and obesity. More recently, cancer therapies-particularly cytotoxic treatments-have been shown to significantly increase the risk of CH. Therapy-related CH, however, exhibits a distinct mutational spectrum, frequently involving genes in the DNA damage response pathway, reflecting the selective pressure exerted by cytotoxic exposure. Current evidence largely supports that cytotoxic therapies primarily drive the expansion of preexisting mutant clones rather than inducing de novo mutations. The increased recognition of therapy-related CH has prompted growing interest in its prognostic and therapeutic implications in patients with cancer. To date, data regarding the prognostic impact of CH in cancer are conflicting, but the presence of CH generally portends worse overall survival, especially among patients with hematologic malignancies. Moreover, cancer survivors with CH appear to be at a heightened risk of cardiovascular disease, which may be further exacerbated by exposure to cardiotoxic cancer therapies. Collectively, these findings underscore the growing clinical relevance of CH and highlight its potential implications for precision medicine and survivorship care in oncology.