Cancers最新文献

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41-45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans.

Background: Computed tomography (CT)-derived body composition parameters, including skeletal muscle and fat indices, are prognosticators in oncology. Most studies focus on baseline body-composition parameters; however, changes during treatment may provide better prognostic value. Standardized methods for measuring/reporting these parameters remain limited.

Methods: This retrospective study included patients who were treated with immunotherapy for non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma between 2017 and 2024 and had technically adequate baseline and follow-up CT scans. Body composition was analyzed using a novel, fully automated software (CompoCT) for L3 slice selection and segmentation. Body composition indices (e.g., skeletal muscle index [SMI]) were calculated by dividing the cross-sectional area by the patient's height squared.

Results: The cohort included 376 patients (mean [SD] age 66.4 [11.4] years, 67.3% male, 72.6% NSCLC, 14.6% RCC, and 12.8% melanoma). During a median follow-up of 21 months, 220 (58.5%) died. Baseline body composition parameters were not associated with mortality, except for a weak protective effect of higher SMI (HR = 0.98, p = 0.043). In contrast, longitudinal decreases were strongly associated with increased mortality. Relative decreases in SMI (HR, 1.17; 95% CI, 1.07-1.27) or subcutaneous fat index (SFI) (HR, 1.11; 95% CI, 1.07-1.15) significantly increased mortality risk. Multivariate models showed similar concordance (0.65) and identified older age, NSCLC tumor type, and relative decreases in SMI and SFI (per 5% units) as independent predictors of mortality.

Conclusions: Longitudinal decreases in skeletal muscle and subcutaneous fat were independent predictors of mortality in immunotherapy-treated patients. Automated CT-based body composition analysis may support treatment decisions during immunotherapy.

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and limited patient compliance hinder widespread adoption. Recent advancements in artificial intelligence (AI) and bowel sound-based signal processing have enabled non-invasive approaches for gastrointestinal diagnostics. Among these, bowel sound analysis-historically considered subjective-has reemerged as a promising biomarker using digital auscultation and machine learning. Objective: This review explores the potential of AI-powered bowel sound analytics for early detection, screening, and characterization of colorectal cancer. It aims to assess current methodologies, summarize reported performance metrics, and highlight translational opportunities and challenges in clinical implementation. Methods: A narrative review was conducted across PubMed, Scopus, Embase, and Cochrane databases using the terms colorectal cancer, bowel sounds, phonoenterography, artificial intelligence, and non-invasive diagnosis. Eligible studies involving human bowel sound-based recordings, AI-based sound analysis, or machine learning applications in gastrointestinal pathology were reviewed for study design, signal acquisition methods, AI model architecture, and diagnostic accuracy. Results: Across studies using convolutional neural networks (CNNs), gradient boosting, and transformer-based models, reported diagnostic accuracies ranged from 88% to 96%. Area under the curve (AUC) values were ≥0.83, with F1 scores between 0.71 and 0.85 for bowel sound classification. In CRC-specific frameworks such as BowelRCNN, AI models successfully differentiate abnormal bowel sound intervals and spectral patterns associated with tumor-related motility disturbances and partial obstruction. Distinct bowel sound-based signatures-such as prolonged sound-to-sound intervals and high-pitched "tinkling" proximal to lesions-demonstrate the physiological basis for CRC detection through bowel sound-based biomarkers. Conclusions: AI-driven bowel sound analysis represents an emerging, exploratory research direction rather than a validated colorectal cancer screening modality. While early studies demonstrate physiological plausibility and technical feasibility, no large-scale, CRC-specific validation studies currently establish sensitivity, specificity, PPV, or NPV for cancer detection. Accordingly, bowel sound analytics should be viewed as hypothesis-generating and potentially complementary to established screening tools, rather than a near-term alternative to validated modalities such as FIT, multitarget stool DNA testing, or colonoscopy.

The cell division cycle machinery has been regarded as a promising therapeutic target for several decades. One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib. These small-molecule therapeutics have exhibited remarkable anti-cancer efficacy and have become primary choices for treating steroid receptor-positive breast cancer at multiple stages. This epoch-making success of cell-cycle-targeting drugs was followed by the development of small molecules to target other cell cycle-regulatory proteins, such as CDK2, CDK1, WEE1 kinase, Aurora kinases, and polo-like kinases, while therapeutic strategies to overcome resistance to CDK4/6 inhibitors have been pursued. In this article, we focus on heterogeneous vulnerabilities of cancers as consequences of various genetic and epigenetic alterations in the cell cycle-regulatory network, and we discuss how next-generation cell-cycle-targeting drugs currently in the developmental pipeline could exploit these heterogeneous vulnerabilities in the cancer cell cycle. We hope to provide a forward-looking perspective on directions for therapeutic cell-cycle targeting in the advent of personalized precision medicine.

Recent advances in molecular pathology, driven by integrated and comprehensive diagnostic approaches, have significantly advanced precision oncology. By leveraging multiomics technologies, molecular pathology enables the simultaneous assessment of genomic alterations, transcriptomic profiles, proteomic activity, and metabolic states integrated with conventional pathological evaluation to better explain tumour biology and behaviour. Large-scale international consortia, including The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC) have systematically demonstrated the value of harmonised multiomics analyses in defining tumour subtypes, uncovering functional dependencies, and generating clinically actionable insights. Evidence from coordinated precision oncology initiatives, such as the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial further indicates that treatment strategies guided by molecular pathology profiling are associated with improved clinical outcomes, including progression-free survival in molecularly selected patient populations. Consequently, molecularly stratified treatment approaches are increasingly required in routine clinical practice to enable targeted therapies for selected tumour entities. Integration of molecular data with functional and clinical outcomes has further facilitated the detection of emerging mechanisms of therapeutic resistance and heterogeneous treatment responses. Importantly, studies have shown that reliance on genomic analysis alone is insufficient to achieve optimal targeted therapy, underscoring the need for multi-layered molecular interrogation. This review highlights the biological and clinical relevance of multiomics integration, emphasising its critical role in comprehensive morpho-molecular tumour assessment and functional analyses while providing clinicians with a practical framework for interpreting integrated molecular diagnostics and addressing the methodological and translational challenges that must be overcome to enable broader implementation of precision oncology in routine practice.

Background/Objectives: The transperineal (TP) approach has progressively replaced the transrectal (TR) approach for prostate biopsy because of its improved safety profile. However, its impact on the detection of clinically significant prostate cancer (csPCa), particularly within modern lesion-focused biopsy strategies that combine targeted and perilesional sampling, remains uncertain. We aimed to evaluate the real-world diagnostic impact of transitioning from a TR systematic-based biopsy strategy to a TP lesion-focused approach. Methods: We conducted a retrospective single-centre study including consecutive men who underwent image-guided prostate biopsy between 2018 and 2025. Only patients with a single MRI-visible lesion (PI-RADS ≥ 3) were included. Two biopsy strategies were compared: TR systematic biopsy (TR-SBx), combining targeted and systematic cores, and TP lesion-focused biopsy (TP-LFx), combining targeted and perilesional cores. The primary outcome was the detection of csPCa (Gleason Grade Group ≥ 2). Secondary outcomes included detection of Gleason Grade Group 1 cancer and negative biopsies. Inverse probability of treatment weighting (IPTW) based on a propensity score was applied to adjust for baseline differences. Doubly robust weighted logistic regression models were used, with predefined subgroup and sensitivity analyses. Results: Among 1032 included patients, 931 underwent TR-SBx and 101 TP-LFx. After restriction to the region of common support, 528 patients were retained for IPTW analyses. In the IPTW-adjusted analysis, TP-LFx was associated with higher csPCa detection compared with TR-SBx (adjusted odds ratio [OR] 2.52, 95% confidence interval [CI] 1.40-4.52; p = 0.002) and with lower detection of Gleason Grade Group 1 cancer (OR 0.50, 95% CI 0.27-0.92; p = 0.03). Subgroup analyses suggested a stronger association in patients with prior negative biopsy and in anterior or apical lesions. Conclusions: In routine clinical practice, transitioning from a transrectal systematic-based biopsy strategy to a transperineal lesion-focused approach was associated with improved detection of csPCa and reduced overdiagnosis. These findings support the consideration of transperineal, lesion-focused MRI-guided biopsy strategies in contemporary prostate cancer diagnostics.

Background/objectives: Physical activity benefits women with metastatic breast cancer. Past trials are typically well-resourced and supervised, but home-based interventions may be preferable and more accessible. This pilot trial evaluated the feasibility and preliminary efficacy of a remotely delivered behaviour change intervention aiming to increase physical activity for women with metastatic breast cancer.

Methods: A 12-week, two-arm trial involved 20 women with metastatic breast cancer randomised 1:1 to a generic recommendation group or behaviour change group. Both groups received a physical activity recommendation, Fitbit^® watch, diary, and nine phone/video call sessions. The behaviour change group received individualised advice around physical activity benefits, motivation, barriers, and social support; the generic recommendation group completed a recurring symptom questionnaire. Feasibility outcomes were recruitment, retention and adherence rates. Acceptability was evaluated with a structured interview at trial completion. Preliminary efficacy outcomes included 5-day Actigraph wear, 6 min walk distance, 30 s sit-to-stands, and questionnaires for self-reported physical activity, quality-of-life, fatigue, behavioural factors, and patient-specific function.

Results: Recruitment, retention, and adherence rates were 63% (n = 20/32), 80% (n = 16/20), and 76% (137/180 sessions), respectively. Participants across both groups reported that participation was acceptable, and their behaviour change was perceived as sustainable. Preliminary change scores for efficacy measures favoured the behaviour change group, except some quality-of-life and behavioural factor subscales.

Conclusions: Participants were receptive to the trial, and feasibility and efficacy measures were positive. This indicates that a behaviour change intervention for unsupervised physical activity is acceptable and can be beneficial to women with metastatic breast cancer, warranting further exploration.

Background/Objectives: Percutaneous microwave (MW) ablation is a nephron sparing treatment for localized renal cell carcinoma (RCC). We compared perioperative, renal functional, and oncologic outcomes for clinical stage 1 RCC treated with MW ablation, PN, or RN. Methods: Adults with clinical T1 kidney masses treated with MW ablation, PN, or RN from 2001-2025 were identified. Outcomes included: 90-day overall and major complication rate, 30-day readmission rate, length of hospital stay (LOS), change in renal function, local recurrence-free survival (LRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS). Univariable and multivariable analyses evaluated outcomes adjusted for confounders. Results: A total of 2201 patients with renal masses ≤ 7 cm and no evidence of locally advanced or metastatic disease were treated with MW ablation (708), PN (729), or RN (764). MW ablation patients were older and more comorbid compared to both PN/RN, whereas RN patients had larger, higher-grade tumors. Ninety-day overall complications were lowest after MW ablation (8.9% vs. 20.3% PN, p < 0.001 and 8.9% vs. 19.9% RN, p < 0.001). LOS was shortest after MW ablation (median 1 day vs. 3 days PN/RN, p < 0.001 for each). Six-month eGFR decline was similar after MW ablation and PN (-5.2% and -4.7%, p = 0.84) but greater after RN (-32.9%, p < 0.001). Local recurrences were more common with MW ablation, with five-year LRFS 96.4% versus 99.7% for PN (p < 0.001). Five-year MFS (99.5% vs. 99.7%, p = 0.24) and CSS (99.3% vs. 99.7%, p = 0.71) did not differ between MW ablation and PN. Conclusions: Percutaneous MW ablation has comparable metastasis free and cancer specific survival with lower perioperative morbidity and comparable renal preservation to PN, despite worse baseline comorbidity and renal function. These findings support MW ablation as an effective nephron-sparing option for appropriately selected patients with clinical T1 RCC when performed at an experienced center.

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10-20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3-4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous.