Search Results (24,289)

Background/Objectives: The latest National Comprehensive Cancer Network (NCCN) Central Nervous System (CNS) Guidelines recommend utilizing next-generation sequencing (NGS) to enable comprehensive genomic profiling (CGP) as the preferred approach for molecular characterization of central nervous system (CNS) malignancies. CNS malignancies present distinct challenges due to the infeasibility of tissue-based testing for many patients and the restrictive nature of the blood–brain barrier (BBB) making plasma-based liquid biopsy an ineffective alternative. Recent advances in liquid biopsy have extended molecular testing beyond plasma to include cerebrospinal fluid (CSF), which serves as a valuable source for tumor-derived nucleic acids. Methods: The Belay Summit™ 2.0 is a high-throughput CGP assay capable of detecting multiple variant types, including single nucleotide variants (SNVs) and small insertion and deletions (Indels), copy number variations (CNVs), gene fusions, splice variants, and immunotherapy biomarkers such as microsatellite instability (MSI) and tumor mutational burden (TMB). This study details the analytical and clinical validation of Summit™ 2.0 to assess its technical performance and clinical sensitivity. Analytical validation was conducted using 68 specimens, demonstrating robust and reproducible detection of all variant types with 15 ng of CSF-derived total nucleic acid (tNA). Results: The analytical sensitivity of the Belay Summit™ 2.0 assay for SNVs and Indels was determined to be 96.7% with a 100% limit of detection (LoD) at a variant allele frequency of 0.3%. Clinical validity was evaluated across a cohort of 118 CSF specimens, including both primary and metastatic CNS tumors, demonstrating 96% sensitivity and 98% specificity. Conclusions: These findings support the use of the Belay Summit™ 2.0 assay for accurate and reproducible genomic profiling of CNS tumors using tumor-derived nucleic acids from CSF in patients for whom tissue-based testing is considered infeasible, unsafe, or not deemed by the prescribing physician to be clinically appropriate. Full article

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody–drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies. Methods: Eligible patients were women with HER2-low or HER2-0 MBC evaluated at MD Anderson between January 2006 and January 2019. HER2-low was defined as either (1) IHC 1+ or (2) IHC 2+ and negative on fluorescence in situ hybridization. Multivariate logistic regression was used to evaluate distinct clinicopathologic features of patients with HER2-low status. Overall survival (OS) was estimated by the Kaplan–Meier method. Multivariate Cox proportional hazards regression was applied to assess the effects of covariates of interest on OS across different HER2 groups. Results: We included 3834 women: 2637 (69%) with recurrent and 1197 (31%) with de novo MBC; HER2-low disease was present in 1575 (60%) and 712 (59%), respectively. In de novo cases, higher nuclear grade was associated with HER2-low status (grade 2 vs. 1, OR = 2.02, p = 0.007; grade 3 vs. 1, OR = 1.87, p = 0.015), while recurrent cases were associated with ER-positivity (OR = 1.96, p < 0.001) and prior adjuvant radiotherapy (OR = 0.79, p = 0.007). Median OS was 3.2 years (95% CI 3.0–3.5). In de novo disease, Black race (HR = 1.48), metaplastic (HR = 3.15) or other non-ductal/lobular histologies (HR = 2.36), and grade 3 (HR = 1.67) predicted worse OS, whereas Hispanic ethnicity (HR = 0.74) and Other races (HR = 0.57), higher ER (HR = 0.48–0.41) and PR (HR = 0.72–0.53), and HER2-low status (HR = 0.77) conferred improved outcomes. In recurrent disease, Black race predicted worse OS (HR = 1.21, 95% CI 1.05–1.39), while Other race (HR = 0.78, 95% CI 0.62–0.97), higher ER (HR = 0.69–0.44) and PR (HR = 0.73–0.73), and HER2-low (HR = 0.89) were protective. HER2 discordance between primary and metastatic sites occurred in 38.8% of recurrent and 13.1% of de novo cases. Conclusions: HER2-low status was significantly associated with longer OS compared to HER2-0 status in both recurrent and de novo MBC cases. These real-world data help establish the prevalence of HER2-low status and its distinct outcomes. The discrepancy in HER2-low status between the primary tumor and metastatic sites highlights the potential for changes in HER2 expression over time, exploring the interaction between HER2-low breast cancer and the tumor microenvironment and emphasizing the importance of monitoring and reassessing HER2 status at various stages to guide treatment decisions effectively and the need for more quantitative and reproducible HER assays. Full article

Background/Objectives: Cancer is a disease with a rising global incidence each year, and an interdisciplinary approach for both its treatment and care is needed. This study aimed to evaluate the effects of a 10-week interdisciplinary integrative oncology group-based program for patients with cancer on quality of life, fatigue, resilience, well-being, anxiety and depression. Methods: This prospective, nonrandomized intervention, waiting-list control group study evaluated the quality of life, fatigue, resilience, anxiety, depression and well-being of a total of 128 patients with cancer (intervention group: n = 86; waiting-list control group: n = 42) at baseline (week 0) and at the end of the observation period (week 10). Results: Compared with patients in the waiting-list group, patients who participated in a 10-week interdisciplinary integrative group program during or after cancer treatment had positive effects on quality of life, social/family well-being, functional well-being, resilience, fatigue, and anxiety. Specifically, significant time × group effects were observed on (FACT-G: p = 0.002, η² = 0.73; FACIT-Fatigue: p = 0.014, η² = 0.47; FACIT-F: p = 0.002, η² = 0.74), social/family well-being (p = 0.015, η² = 0.46), functional well-being (p < 0.001, η² = 0.102), with a large effect size and resilience mean scores (p = 0.003, η² = 0.069), and anxiety mean scores (p = 0.005, η² = 0.060), with a medium effect size. Conclusions: This study revealed that compared with nonparticipants, participants in the 10-week interdisciplinary program benefited more from the program. Full article

Background: Mutations in the KRAS gene play a pivotal role in lung cancer development and progression and are becoming increasingly important in therapeutic decision-making. The detection of these mutations in circulating tumor DNA (ctDNA) has attracted attention as a minimally invasive diagnostic approach. However, the accuracy reported in different studies varies widely. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA-DTA guidelines. Eligible studies evaluated the detection of KRAS mutations in ctDNA in plasma or serum for lung cancer diagnosis and reported sufficient data to construct 2 × 2 contingency tables. Primary pooled estimates of sensitivity, specificity and likelihood ratios were calculated using aggregated 2 × 2 contingency tables. Additionally, a bivariate random-effects model was applied in a secondary analysis to investigate between-study heterogeneity. Results: Nine diagnostic study arms comprising 691 patients met the inclusion criteria. Across all datasets, there were 255 true positives, 19 false positives, 136 false negatives, and 281 true negatives. The pooled sensitivity was 65.2%, while the pooled specificity was 93.7%. The positive likelihood ratio was 10.35, and the negative likelihood ratio was 0.37, resulting in a diagnostic odds ratio of 28.0, which indicates strong rule-in capability. Sensitivity showed moderate heterogeneity across studies. In contrast, specificity demonstrated minimal heterogeneity. Conclusions: ctDNA-based detection of KRAS mutations demonstrates high specificity but moderate sensitivity for diagnosing lung cancer. These findings suggest that a KRAS liquid biopsy could be a valuable complementary diagnostic tool, particularly when a tissue biopsy is not possible or is inadequate, and it could support more personalized decision-making as analytical technologies continue to advance. Full article

Pseudouridine (Ψ), the most abundant RNA modification, plays essential roles in shaping RNA structure, stability, and translational output. Beyond cancer, Ψ is dynamically regulated across numerous physiological and pathological contexts—including immune activation, metabolic disorders, stress responses, and pregnancy-related conditions such as preeclampsia—where elevated Ψ levels reflect intensified RNA turnover and modification activity. These broad functional roles highlight pseudouridylation as a central regulator of cellular homeostasis. Emerging evidence demonstrates that Ψ dysregulation contributes directly to the development and progression of several women’s cancers, including breast, ovarian, endometrial, and cervical malignancies. Elevated Ψ levels in tissues, blood, and urine correlate with tumor burden, metastatic potential, and therapeutic responsiveness. Aberrant activity of Ψ synthases such as PUS1, PUS7, and the H/ACA ribonucleoprotein component dyskerin alters pseudouridylation patterns across multiple RNA substrates, including rRNA, tRNA, mRNA, snoRNAs, and ncRNAs. These widespread modifications reshape ribosome function, modify transcript stability and translational efficiency, reprogram RNA–protein interactions, and activate oncogenic signaling programs. Advances in high-resolution, site-specific Ψ mapping technologies have further revealed mechanistic links between pseudouridylation and malignant transformation, highlighting how modification of distinct RNA classes contributes to altered cellular identity and tumor progression. Collectively, Ψ and its modifying enzymes represent promising biomarkers and therapeutic targets across women’s cancers, while also serving as sensitive indicators of diverse non-cancer physiological and disease states. Full article

Short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, are the result of microbial fermentation and have been demonstrated to exert anticancer effects in different experimental models. We systematically reviewed 27 studies on postbiotics in colorectal cancer models, enclosing a range of study types including cell lines, animal models, and organoids. Eight studies that focused specifically on SCFAs were identified and analyzed. SCFAs promoted apoptosis through caspase activation, influenced NF-κB and MAPK signaling, increased mucin expression, and strengthened barrier function. Butyrate has also been demonstrated to induce autophagy via LKB1–AMPK signaling. Studies using SCFA-containing supernatants showed similar effects, although the presence of multiple biomolecules limited attribution. Overall, these findings provide a robust foundation for further research, particularly in the context of translational studies that can bridge the gap between preclinical and clinical research. Full article

Objectives: Among people with HIV (PWH), the epidemiology of malignant tumors has shifted from AIDS-defining malignancies (ADMs) to non-AIDS-defining malignancies (NADMs). This study examined temporal changes in the standardized incidence ratio (SIR) of malignant tumors in an HIV cohort in Japan. Methods: A retrospective cohort study was conducted of 3793 men treated for HIV at Osaka National Hospital between 2007 and 2024. Diagnoses of malignant tumors were identified from medical records and the expected numbers of cases were calculated using cancer incidence rates for the general male population of Japan. SIRs and 95% confidence intervals (CIs) were calculated and temporal changes across four periods (2007–2011, 2012–2016, 2017–2020, and 2021–2024) were evaluated using the p for trend. Results: The overall SIR for malignant tumors decreased from 5.12 (95% CI: 4.02–6.43) in 2007–2011 to 0.86 (95% CI: 0.64–1.14) in 2021–2024, mainly owing to a decline in ADMs (SIR: 111.93 to 5.70), including Kaposi’s sarcoma (SIR: 4269.39 to 547.26) and AIDS-related lymphoma (SIR: 62.18 to 3.13). The overall SIR for NADMs was similar to that of the general population (1.04; 95% CI: 0.89–1.22), and decreased from 1.64 to 0.69, but the risks of anal cancer (SIR 40.63) and oral/pharyngeal cancer (SIR 3.16) remained high. Conclusions: Among men with HIV in Japan, the overall risk of ADMs and NADMs has decreased; however, the risk of specific NADMs remains high. Cancer prevention strategies for PWH need to focus on high-risk NADMs. Full article

Over the last decades, a significant improvement in cancer patient outcomes has occurred due to advances in cancer cell biology, systemic immunity, tumor-immune microenvironment (TIME) and precision cancer therapy. Despite this explosion of knowledge, its usefulness in clinical practice has been limited by the ability to translate multidimensional data into clinical care. Progress in artificial intelligence (AI) opens up a new frontier, with the promise of achieving synergistic and comprehensive integration. The classification of cancer biology and immunobiology into hallmarks of cancer by Hanahan and Weinberg provides a framework for organizing this information. This systematic classification has enabled the understanding of the interplay and cross-talk between its parts. Targeted cancer therapies and immunotherapies have achieved considerable success, yet their combinatorial potential is still being uncovered. Molecular diagnostics has worked hand-in-hand with precision oncology in deploying new therapies in a cancer-informed and patient-specific way. Harnessing the full power of the advances in these three fields with the aid of AI promises a transformation of molecular diagnostics. This review conceptualizes molecular diagnostics in the context of cancer hallmarks using nonsmall cell lung cancer (NSCLC) as a template, highlighting the potential of a new diagnostic science through the integrative power of AI. Full article

Melanoma is highly dangerous and can spread rapidly to other parts of the body. It has an increasing fatality rate among different types of cancer. Timely detection of skin malignancies can reduce overall mortality. Therefore, clinical screening methods require more time and accuracy for diagnosis. An automated, computer-aided system would facilitate earlier melanoma detection, thereby increasing patient survival rates. This paper identifies melanoma images using a Convolutional Neural Network. Skin images are preprocessed using Histogram Equalization and Gabor transforms. A Gabor filter-based Convolutional Neural Network (CNN) classifier trains and classifies the extracted features. We adopt Gabor filters because they are bandpass filters that transform a pixel into a multi-resolution kernel matrix, providing detailed information about the image. This study suggests a method with accuracy, sensitivity, and specificity of 98.58%, 98.66%, and 98.75%, respectively. This research supports SDGs 3 and 4 by facilitating early melanoma detection and enhancing AI-driven medical education. Full article

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs. Full article

A key function of naturally occurring antibodies is to control pathologically altered cells, such as those with aberrant glycosylation. Age-related diminution in the pool of B cells producing these immunoglobulins is linked to impaired anti-tumor immunity. In this study, the levels of antibodies against tumor-associated carbohydrate antigens (TACAs)—common in gastric cancer (GC) and other malignancies—were analyzed in 235 treatment-naïve GC patients (stages I–IV) and 76 healthy donors using a printed glycan array (PGA). We found that anti-glycan IgM levels, but not IgG, reduced with age in both patients and donors. Crucially, IgM levels against most glycans were significantly lower in the GC cohort compared with healthy donors, a trend that remained after age adjustment. Furthermore, an immunohistochemical analysis revealed that human anti-GalNAcα (Tn) antibodies—a well-characterized TACA in gastrointestinal cancers—bound to tumor cells and exhibited perinuclear and membrane staining in non-tumor surface cells within the same organ. These data support the hypothesis that gastric cancer patients have reduced levels of anti-glycan IgMs, which are responsible for the early recognition of transformed cells. This specific immunodeficiency may contribute to a permissive environment for tumor development. Full article

Background/Objective: High-risk Human papillomavirus (hrHPV) is the leading cause of premalignant lesions and cervical cancer (CC), affecting disproportionally women living with HIV. Mozambique is among the countries with a heavy triple-burden of HIV, hrHPV infections and CC which accounts for more than 5300 new cases and 3800 deaths each year. In this study, we assessed the age-specific distribution and factors associated with hrHPV and cervical lesions among HIV-positive and -negative women from HPV-ISI (HPV Innovative Screening Initiative) study in Maputo, Mozambique. Methods: This cross-sectional study included 1248 non-pregnant women aged ≥18 years who attended CC screening at the DREAM Sant’Egídio Health Centre between July 2021 and April 2022. Screening involved visual inspection with acetic acid (VIA) and high-risk HPV DNA testing. Sociodemographic, lifestyle, and reproductive data were collected through a routine questionnaire. Logistic regression assessed associations between risk factors and hrHPV infection or cervical lesions. Age-specific hrHPV prevalence, partial HPV16/18 genotyping, and abnormal cytology rates were further analyzed by HIV status. Results: The mean age of participants was 43.0 ± 8.6 years. Overall hrHPV prevalence was 28.0%, being higher among HIV-positive women (46.8%) than HIV-negative women (23.8%). Non-16/18 hrHPV genotypes predominated across all age groups. VIA positivity was 11.1%, most frequently involving less than 75% of the cervical area and was more common among younger women (30–45 years) and those living with HIV. Increasing age was associated with lower odds of hrHPV infection (OR = 0.98, 95% CI: 0.97–1.00; p = 0.017), as was higher parity (≥3 deliveries vs. nulliparity: OR = 0.58, 95% CI: 0.36–0.94; p = 0.029). Contraceptive use (OR = 1.65, 95% CI: 1.15–2.38; p = 0.007) and a partially or non-visible squamocolumnar junction (SCJ) (OR = 2.88, 95% CI: 1.74–4.79; p < 0.001) were associated with higher odds of VIA positivity. Conclusions: hrHPV infection and cervical lesions were more frequent in younger and HIV-positive women, highlighting the need for strengthened targeted screening within HIV care services in Mozambique. Full article

Evaluating the activity of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan (Trp) metabolism, is important because IDO is involved in immune tolerance and drives the production of Trp metabolites implicated in psychiatric disorders and cancer. This study aimed to design and develop a novel fluorescent l-Trp derivative to fluorometrically monitor Trp-catabolizing enzyme activity via IDO. To evaluate IDO activity in vivo, 7-N,N-dimethylamino-2,1,3-benzoxadiazole (DBD), a fluorophore, was covalently bound at the 5-position of the indole ring in Trp to produce 5-DBD-l-Trp. An in vivo microdialysis (MD) study was conducted using the kidneys of Sprague–Dawley rats. Specifically, 5.0 μM 5-DBD-l-Trp in phosphate-buffered Ringer’s solution was infused into the rats, and the MD sample was analyzed via high-performance liquid chromatography with fluorescence detection. In the MD sample, two fluorescence peaks other than 5-DBD-l-Trp were observed during the 5-DBD-l-Trp infusion, and the main metabolite peak was proposed to be 5-DBD-kynurenine, verified by liquid chromatography-tandem mass spectrometry. The intensity of the fluorescent peak was significantly attenuated by co-infusion with an IDO inhibitor, 1-methyl-d-Trp. These results suggest that 5-DBD-l-Trp may be metabolized by renal IDO and can be used to evaluate IDO activity in vivo. Full article

Estrogen receptor-positive (ER⁺) breast cancer represents the most prevalent molecular subtype of breast cancer, characterized by hormone-dependent growth, relatively indolent progression, and a pronounced tendency to metastasize to bone. While endocrine therapies remain the cornerstone of treatment, a significant proportion of ER⁺ tumors eventually develop resistance, culminating in distant metastases—most frequently to the bone. Bone metastasis substantially compromises patient survival and quality of life, highlighting the critical need to elucidate its molecular underpinnings. Recent multi-omics and mechanistic studies have shed light on the complex interplay between tumor-intrinsic signaling pathways, such as dysregulated ER signaling, PI3K/AKT/mTOR, TGF-β, and Hippo pathways, and the bone microenvironment, including osteoclast activation, immune suppression, and stromal remodeling. This review systematically summarizes the current understanding of the molecular mechanisms driving bone metastasis in ER⁺ breast cancer, with a particular focus on tumor–bone microenvironment crosstalk and key regulatory pathways. Additionally, we discuss recent advances in therapeutic strategies, encompassing next-generation endocrine therapies, CDK4/6 inhibitors, bone-targeted agents, and pathway-specific inhibitors. Together, these insights pave the way for more effective and personalized interventions against ER⁺ breast cancer with bone involvement. Full article

Familial cancers are caused by inherited mutations in specific genes that regulate cell growth, division, and repair. Approximately 5–10% of all cancer cases have a hereditary component, where germline mutations in certain genes increase an individual’s susceptibility to developing cancer. Two major categories of genes are involved in cancer development: tumour suppressor genes and oncogenes. Both play critical roles in regulating normal cell behaviour, and when mutated, they can contribute to uncontrolled cell proliferation and tumour formation. In addition to genetic mutations, epigenetic alterations also play a significant role in familial cancer. Epigenetics refers to changes in gene expression due to DNA methylation, histone modifications, and the dysregulation of non-coding RNAs without alter the underlying DNA sequence. Familial cancer syndromes follow various inheritance patterns, including autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance, each with distinct characteristics. Identifying genetic mutations associated with familial cancers is a cornerstone of genetic counselling, which helps individuals and families navigate the complex intersection of genetics, cancer risk, and prevention. Early identification of mutations enables personalized strategies for risk reduction, early detection, and, when applicable, targeted treatment options, ultimately improving patient outcomes. Full article