搜索结果：Oncology research

Digital twin technology represents a transformative approach in healthcare, creating virtual replicas of physical entities that enable real-time data integration, predictive modelling, and personalised treatment strategies. In urology, this emerging technology offers unprecedented opportunities to optimise patient care through simulation-based decision-making. This narrative review comprehensively examines current applications of digital twin technology in urology, evaluates its clinical utility across various urological conditions, and identifies key challenges limiting its widespread implementation. A comprehensive search was conducted across PubMed, Web of Science, and Scopus databases for literature published between January 2020 and January 2026. Search terms included digital twin, virtual twin, urology, uro-oncology, prostate cancer, renal surgery, and bladder dysfunction. Studies focusing on the development, validation, and clinical implementation of digital twins in urological practice were included. Digital twin technology demonstrates significant potential in uro-oncology for treatment planning, surgical navigation, and disease progression monitoring. Key applications include patient-specific tumour growth simulation in prostate cancer, three-dimensional anatomical modelling for partial nephrectomy, and bladder function prediction in outlet obstruction. Integration with artificial intelligence enhances predictive accuracy and enables real-time surgical guidance. Digital twin technology represents a paradigm shift towards precision urology, though challenges in data integration, computational requirements, validation, and ethical considerations must be addressed before routine clinical implementation. Future developments should focus on standardisation, regulatory frameworks, and prospective clinical validation studies.

Recently, various basic research and clinical studies have revealed the further potential of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor Olaparib and histone deacetylase inhibitor Chidamide in lung cancer. However, no research available was found to report whether there is a synergistic effect of Olaparib in combination with Chidamide. This research was conducted to investigate whether there is a synergistic effect between the two drugs and the underlying mechanism in lung cancer cell lines. Here, we treat lung cancer cell lines with Olaparib with or without Chidamide in vivo and in vitro. Based on that, we found that there were synergistic effects between Olaparib and Chidamide. Combined use of them cooperatively downregulated the expression of MYBL2, which was responsible for the downregulation of BRCA1, a main member of DNA damage repair. Simultaneously, Olaparib-induced inhibition of PARP expression leads to the 'synthetic lethality' of cells. On the other hand, MYBL2 may regulate the expression of cycle protein dependent kinase 1, causing G2M cell cycle arrest. Consequently, the combination of Olaparib and Chidamide synergistically induces cell apoptosis through synthetic lethality and cell cycle arrest to exert an antitumor effect.

Integration of Artificial Intelligence (AI), particularly deep learning, into medical imaging represents a profound shift in diagnostic medicine, moving from purely descriptive analysis to advanced predictive and prescriptive analytics. This Collection explores the rapid advancement of AI-driven tools in their specific fields such as oncology, cardiology, ophthalmology and so on, highlighting their potential to improve diagnostic accuracy, workflow efficiency, and personalized treatment planning. However, significant challenges remain, including the heterogeneity of medical image data, the "black box" nature of some intelligent models, and the critical hurdles of clinical integration and validation. The research presented here addresses these frontiers, showcasing innovations in algorithm development, explainable AI, and translational application. This Editorial synthesizes the contributions and outlines the essential collaborative pathway-uniting computer scientists, clinicians, and regulatory bodies-required to translate algorithmic promise into robust, trustworthy, and equitable clinical tools that genuinely improve patient care.

Covalent Bruton tyrosine kinase (BTK) inhibitors have advanced the treatment of Waldenström macroglobulinaemia; however, the occurrence of progression, intolerance, and acquired resistance are not fully understood. We aim to report on the safety and activity of pirtobrutinib (a highly selective, non-covalent BTK inhibitor) in patients with relapsed or refractory Waldenström macroglobulinaemia, including those who received previous covalent BTK inhibitors as part of the phase 1/2 BRUIN trial. The BRUIN study was an open-label, multicentre, phase 1/2 trial that enrolled patients with relapsed or refractory B-cell malignancies from 29 sites across eight countries. Patients aged 18 years or older who previously received BTK inhibitor-containing regimens, had an Eastern Cooperative Oncology Group performance status of 0-2, and histologically confirmed Waldenström macroglobulinaemia were eligible. In phase 1, patients received 100-300 mg oral pirtobrutinib once a day in 28-day cycles and the recommended phase 2 dose (RP2D) of 200 mg pirtobrutinib once a day was determined. The phase 2 primary endpoint was antitumour activity of pirtobrutinib based on objective response rate as assessed by an investigator in patients with chronic lymphocytic leukaemia, small lymphocytic leukaemia, or mantle cell lymphoma. In patients with Waldenström macroglobulinaemia, response was evaluated using the Sixth International Workshop on Waldenström Macroglobulinemia (IWWM-6) criteria. BRUIN is registered with ClinicalTrials.gov, NCT03740529 (completed). BRUIN recruited patients from Aug 12, 2019, to March 14, 2022, and 778 patients received pirtobrutinib. 80 patients had relapsed or refractory Waldenström macroglobulinaemia (n=18 in phase 1 and n=62 in phase 2), with a median age of 68·5 years (IQR 61·0-75·0). 52 (65%) patients were male and 28 (35%) were female. The median number of previous lines of systemic therapy was 3·0 (2·0-5·0). 63 (79%) patients received previous covalent BTK inhibitors. 73 (91%) received 200 mg pirtobrutinib once per day (the RP2D). Using IWWM-6 criteria, the objective response rate was 82·5% (95% CI 72·4-90·1), with one (1·3%) patient reaching complete response, eight (10·0%) reaching very good partial response, 49 (61·3%) reaching partial response, and eight (10·0%) reaching minor response. The median study follow-up was 35·0 months (17·7-47·7). The objective response rate was 81·0% (69·1-89·8) for those who received previous covalent BTK inhibitors and 88·2% (63·6-98·5) for covalent BTK inhibitor-naive patients. Grade 3 or higher treatment-emergent adverse events occurred in 57 (71%) patients, with the most common being neutropenia or neutrophil count decreased (15 [19%]) and anaemia (19 [24%]). Treatment-emergent deaths were reported in five (6%) patients (bacterial sepsis, intracranial haemorrhage, COVID-19 pneumonia, hypertensive cardiomegaly and pneumonia [n=1 each unrelated to treatment], and treatment-related necrotising pneumonia [n=1]). Treatment-emergent adverse events leading to dose reductions occurred in four (5%) patients and pirtobrutinib discontinuation in 12 (15%). Pirtobrutinib was highly active and well tolerated, regardless of previous exposure to covalent BTK inhibitors, and might be a promising new therapeutic option for patients with relapsed or refractory Waldenström macroglobulinaemia, particularly in those previously exposed to covalent BTK inhibitors, for whom durable and effective treatments are needed. Eli Lilly and Company.

Brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (A-AVD) improves outcomes in advanced-stage classic Hodgkin lymphoma, but patients with a positive early interim PET have inferior prognosis. We evaluated whether very early [18F]fluorodeoxyglucose ([18F]FDG)-PET-guided treatment adaptation after one cycle of A-AVD improves activity while limiting exposure to intensive chemotherapy. This single-arm, multicentre, phase 2 trial was conducted at 16 centres in seven countries (the Netherlands, Spain, Denmark, Belgium, Portugal, Slovakia, and Poland). Adults aged 18-60 years with previously untreated advanced-stage classic Hodgkin lymphoma, WHO performance status 0-2, and adequate organ function received one cycle of A-AVD (brentuximab vedotin 1·2 mg/kg intravenously, doxorubicin 25 mg/m2 intravenously, vinblastine 6 mg/m2 intravenously, and dacarbazine 375 mg/m2 intravenously, all on days 1 and 15), followed by centrally reviewed [18F]FDG-PET-CT (PET1). PET1-negative (Deauville score 1-3) patients received five additional A-AVD cycles; PET1-positive (Deauville score 4-5) patients switched to six cycles of BrECADD (brentuximab vedotin 1·8 mg/kg intravenously on day 1; etoposide 150 mg/m2 intravenously on days 2-4; cyclophosphamide 1250 mg/m2 intravenously on day 2; doxorubicin 40 mg/m2 intravenously on day 2; dexamethasone 40 mg orally on days 2-5; dacarbazine 250 mg/m2 intravenously on days 3-4). The primary endpoint was 2-year modified progression-free survival (mPFS), defined as the proportion of patients alive and free of progression, relapse, or death from treatment start, with initiation of new systemic therapy for persistent disease counted as an event. Analyses were prespecified and conducted in the evaluable population (registered and eligible patients, who commenced the allocated treatment according to PET1 results after 1 cycle of A-AVD). The safety population consists of all patients who started A-AVD treatment (ie, received at least one dose of study therapy). This is the primary analysis of a completed trial. This trial is registered on ClinicalTrials.gov (NCT03517137) and EudraCT 2017-000498-35). From Aug 1, 2019, to Aug 31, 2021, we enrolled 150 patients (81 males [54%] and 69 females [46%]; median age 32 years [IQR 23-39]) who received one cycle of A-AVD, after which 90 (60%) of them had a negative PET1 and 60 (40%) a positive result. 145 were evaluable for efficacy; the median follow-up at the clinical cutoff (Sept 1, 2023; database lock Dec 11, 2023) was 30·1 months (IQR 24·6-36·4). 16 patients experienced an mPFS event. The estimated 2-year mPFS was 89·5% (80% CI 85·7-92·4). The most common grade 3-4 adverse event was neutropenia (53 [35%] of 150) followed by anaemia (18 [12%]) and peripheral sensory neuropathy (nine [6%]). Serious adverse events occurred in 45 (30%) of 150 patients. No deaths occurred. Very early PET-guided intensification with BrECADD yields high activity in advanced-stage classic Hodgkin lymphoma while sparing most patients intensive chemotherapy. Takeda Oncology.

Pancreatic ductal adenocarcinoma (PDAC) is frequently preceded by new-onset diabetes mellitus (NODM), yet differentiating PDAC-associated DM from type 2 diabetes (T2D) remains clinically challenging. We investigated whether plasma proteomic profiling combined with machine learning could discriminate these conditions. Plasma samples from individuals with PDAC (with and without DM), long-standing T2D, and controls were analyzed by MALDI-TOF mass spectrometry. Spectral features were processed through a nested cross-validation framework to prevent data leakage, and model interpretability was explored using SHAP values. In parallel, low-molecular-weight proteins were characterized by GeLC-MS followed by LC-MS/MS and differential abundance analysis. Machine learning models distinguished PDAC-associated DM from T2D with a balanced accuracy of 85%. Proteomic analyses identified distinct signatures in PDAC- associated DM, including downregulation of erythrocyte-related proteins and PPBP, and upregulation of acute-phase reactants such as FGA, CP, and SERPINA3. Treatment-naïve cases displayed increased circulating epithelial and keratin-associated proteins, which were attenuated after therapy, suggesting dynamic tumor-related remodeling. These findings demonstrate that integrating MALDI-TOF profiling with machine learning can capture plasma signatures associated with PDAC-associated DM. Although exploratory, this approach supports further validation in prospective cohorts aimed at improving PDAC risk stratification among individuals with NODM. SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a dismal 5-year survival rate, primarily due to late-stage diagnosis. The frequent occurrence of new-onset diabetes mellitus (NODM) as a paraneoplastic syndrome offers a critical window for early detection. However, the clinical challenge of distinguishing PDAC-associated diabetes (PDAC-DM) from type 2 diabetes mellitus (T2D) has hindered the implementation of effective screening strategies. This study addresses this significant clinical problem by leveraging a multi-faceted proteomics approach. We demonstrate that the integration of MALDI-TOF mass spectrometry peptide profiling with machine learning algorithms can accurately discriminate PDAC-DM from T2D with 85% accuracy. Furthermore, we used LC-MS/MS to identify specific low molecular weight proteins that are differentially regulated between these conditions, providing a molecular basis for the observed discrimination. Our work is significant as it presents a novel, high-throughput pipeline for biomarker discovery that combines the scalability of MALDI-TOF with the analytical power of LC-MS/MS and machine learning. The identified plasma signatures hold strong translational potential to improve risk stratification in patients with new-onset diabetes, ultimately enabling earlier diagnosis of PDAC and improving patient survival prospects. This research directly contributes to the field of clinical proteomics by providing a robust methodological framework and candidate biomarkers for the early detection of one of oncology's most challenging diseases.

Antibody-drug conjugates (ADC) have emerged as an important part of systemic treatment across disease sites. To date, there is no robust pooled prevalence estimate of nausea and vomiting induced by ADCs. Establishing such estimates is essential to determine if ADC-induced nausea and vomiting (ADCINV) represents a clinically significant problem warranting further research into antiemetic prophylaxis. Our aim is to report the prevalence of reported ADCINV across literature. A systematic search of Medline, Embase, Cochrane CENTRAL and Web of Science was conducted from database inception until September 24, 2025. Articles were included if they reported nausea and/or vomiting due to ADCs used in cancer treatment, in the abstract. Pooled prevalence was reported. Subgroup analysis was conducted by ADC. Meta-regression was conducted by age and sex. Quality assessment was conducted. Type I error was set at 0.05. A total of 209 studies with 15,493 patients were included. Thirty-nine percent (95%CI, 36-42%) of patients experience any nausea, and 26% (95%CI, 23-29%) experience any vomiting. Younger patients are more likely to experience nausea; each 10-year increase in age is associated with a 12% decrease in nausea rates. Higher emetogenic ADCs include trastuzumab deruxtecan, sacituzumab govitecan, brentuximabvedotin and patritumab deruxtecan. Lower emetogenic agents include disitimab vedotin, telisotuzumab vedotin and rovalpituzumab tesirine. This is the first study to report prevalence of ADCINV across ADCs. It is a prevalent adverse effect akin to chemotherapy-induced nausea and vomiting that should be viewed as clinically relevant and further investigated to help develop optimal strategies related to antiemetics.

Over recent decades, cutaneous melanoma (CM) incidence in the United States (US) has increased but now appears to be plateauing, whereas mortality has declined. However, much less is known about how CM incidence and mortality vary between states, or about how differences between states in incidence relate to lifestyle factors, ambient UV exposure, and prevention or health care resources. At the population level, most studies have compared overall CM incidence and mortality across broad racial and ethnic groups without describing age-specific or state-specific patterns. This lack of granularity limits our understanding of when and where different population groups bear the greatest CM burden and where targeted prevention and early detection efforts are most needed. We conducted a cross-sectional study of the incidence and mortality trends of CM in the US from 2001 to 2019, including state-level analyses of temporal trends and ecological correlates, as well as national population-level analyses by age, sex, and race/ethnicity. Annual percent change (APC) and average annual percent change (AAPC) were calculated, and ecological correlations and multivariable linear regression models were fitted with state-level AAPC in CM incidence as the outcome. Between 2001 and 2016, CM incidence increased significantly (APC, 1.95% [95% CI, 1.67% to 2.24%], p&#x2009;<&#x2009;0.001) and then stabilized from 2016 to 2019 (APC, -0.59% [95% CI, -3.36% to 2.27%], p&#x2009;=&#x2009;0.662). During the study period, mortality declined significantly (AAPC, -1.52% [95% CI, -2.38% to -0.66%], p&#x2009;<&#x2009;0.001). A persistent upward incidence trend was observed in 24 states, predominantly in the Midwest and Southern regions. The incidence rate ratio (IRR) between the highest- and lowest-rate states increased from 2.63 in 2001 to 4.85 in 2019, whereas the mortality rate ratio (MRR) narrowed to 1.19 by 2019. In ecological analyses, higher state-level obesity prevalence and lower physical activity level were each associated with higher AAPC in CM incidence, whereas higher personal doctor rates were inversely associated. Average daily solar insolation and tanning/sunscreen policies were not significantly related to the AAPC. Across all racial/ethnic groups, CM incidence was higher in young women than in young men, with sex-specific crossover ages varying by race/ethnicity, while young men consistently experienced higher mortality. Age-stratified analyses showed that disparities in CM incidence and mortality rates between non-Hispanic Whites and other races/ethnicities were more pronounced in young individuals than in the elderly. There was also substantial interstate variation in incidence rate ratios comparing non-Hispanic Whites with other racial/ethnic groups. Despite overall plateauing incidence and declining mortality, CM remains highly unequal across states and population groups. Interstate incidence disparities widened over time, with marked variation by age, sex, and race/ethnicity. These findings provide a more detailed picture of geographic and population-level disparities in CM and may help inform future surveillance, risk stratification, and hypothesis-driven prevention research.

Autosomal dominant acute porphyrias are rare inherited disorders of haem biosynthesis characterised by accumulation of potentially neurotoxic porphyrin precursors and attacks of severe abdominal pain with autonomic and neuropsychiatric features. Disease severity ranges from asymptomatic individuals to those with recurrent, life-threatening attacks. The International Porphyria Network invited 34 acute porphyria specialists from 17 countries to form an expert panel. The invited group included clinicians from diverse specialities (ie, internal medicine, haematology, endocrinology, gastroenterology, hepatology, neurology, and biochemistry), together with laboratory scientists and patient representatives. The panel met online (in 2023-25) to develop 15 evidence-based recommendations with the use of the Grading of Recommendations, Assessment, Development, and Evaluations framework addressing attack prevention, management of sporadic and recurrent attacks, long-term follow-up, surveillance for primary liver cancer, and family screening. The guidelines support safe, consistent clinical care and improved outcomes, recognising global variation in resources and access to high-cost drugs, and highlighting priorities for future research.

Patients diagnosed with cancer are at risk of viral reactivation, namely herpes simplex virus (HSV), varicella-zoster virus (VZV) and/or cytomegalovirus (CMV). However, the risk varies significantly with underlying malignancy and treatment regimen. We review the latest evidence for antiviral prophylaxis strategies, focusing on novel immune therapies and future directions. Antiviral prophylaxis is indicated for all high-risk patients. The approval of letermovir for CMV prophylaxis has significantly reduced the burden of clinically significant infections in allogeneic hematopoietic stem cell transplant (alloHCT) recipients, and recent data now supports use up to 200 days posttransplant. For intermediate-risk regimens such as myeloma therapies and autologous hematopoietic stem cell transplant (autoHCT), antiviral prophylaxis is also a cornerstone of VZV prevention. Newer chimeric antigen receptor (CAR) T-cell and bispecific antibody (BsAb) therapies are increasingly available; while HSV/VZV prophylaxis has been incorporated into trial and real-world treatment protocols, optimal duration is unclear and data on CMV reactivation is still emerging. Solid tumours are a lower risk cohort, but high-dose steroids, immune checkpoint inhibitors and radiotherapy can increase the risk of viral reactivation and, therefore, close clinical monitoring is warranted. As the cancer treatment landscape evolves, ongoing research into optimal antiviral prophylaxis approaches is necessary to improve patient outcomes.

High bone mineral density (BMD) is common and sometimes an incidental finding. The causes are numerous. Among them, none has previously been attributed to total body irradiation (TBI). We present the case of a 56-year-old female patient with a history of T-lymphoblastic lymphoma at age 33 who was treated with allogeneic hematopoietic stem cell transplantation following a conditioning regimen including a single-fraction 10 Gray TBI. This patient was in complete remission but experienced several transplant-related late effects. She presented to the rheumatology outpatient clinic with chronic mechanical low back pain and a history of early menopause. Bone assessment by densitometry revealed high bone mineral density with a lumbar spine L2-L4 T-score of +6.3 standard deviation (SD) (1.939 g/cm&#xb2;), right femoral neck T-score of +7.2 SD (1.849 g/cm&#xb2;), right total femur T-score of +4 SD (1.484 g/cm&#xb2;), distal radioulnar T-score of +0.7 SD (0.495 g/cm&#xb2;). Imaging revealed sclerotic lesions in the vertebrae, femoral cortices and pelvis. An etiological workup excluded other causes such as fluorosis, mastocytosis, renal osteodystrophy, hypoparathyroidism/pseudohypoparathyroidism and myelofibrosis. Bone growth factors and resorption markers were normal. Genetic sequencing showed no significant abnormalities. Based on this comprehensive evaluation, TBI was identified as a possible contributing factor to the occurrence of high BMD. The patient was managed with analgesics and regular follow-up. This case highlights the importance of a systematic etiologic approach to high bone mineral density and underscores the need for future scientific research to better understand this phenomenon for which the pathological relationship with radiation exposure remains unknown.

Leech therapy is used in diverse ways in the medical field, such as for flap salvation and for treatment of osteoarthritis. While bleeding is a recognized adverse effect, severe coagulopathy is rare and underreported, especially when compounded by concurrent anticoagulant use. We present a case of a 76-year-old female undergoing leech therapy in combination with systemic heparin for free flap salvage following partial glossectomy and neck dissection. Shortly after initiating both therapies, the patient developed marked coagulopathy, evidenced by prolonged activated partial thromboplastin time (aPTT), elevated thrombin time, and persistent bleeding from the surgical site. Laboratory results suggested synergistic anticoagulant effects of heparin and hirudin, the potent direct thrombin inhibitor secreted by medicinal leeches. Despite discontinuation of systemic heparin, bleeding persisted until leech therapy was halted. The patient received 8 units of packed red blood cells (pRBCs) during the treatment course. Coagulation markers normalized after cessation of leech therapy, with no further bleeding events. This case highlights a potentially underrecognized risk of coagulopathy in patients undergoing combined leech and systemic anticoagulation therapy. The mechanistically distinct pathways of heparin and hirudin may act synergistically to impair both free and clot-bound thrombin activity. Given the absence of formal guidelines for coagulopathy monitoring in such cases, we propose daily assessment of coagulation markers including aPTT, PT/INR, and a one-time measurement of thrombin time and anti-Xa levels after treatment initiation. This report underscores the need for standardized protocols and further research to guide safe implementation of leech therapy, particularly in patients receiving systemic anticoagulation.

Over the past several decades, immunotherapy has emerged as a transformative paradigm in oncology. Within this domain, vaccines targeting tumor-specific neoantigens represent one of the most advanced approaches, engineered to activate the host immune system and elicit potent, antigen-specific T-cell responses. By stimulating both CD8+ cytotoxic and CD4+ helper T cells, these vaccines enable highly selective tumor cell elimination while establishing durable immunological memory. Despite their promise, the rational development and clinical translation of neoantigen-based vaccines remain constrained by substantial challenges that limit their broad therapeutic impact. This review provides a comprehensive synthesis of the field, tracing the entire pipeline from the molecular origin and computational prediction of neoantigens to the design principles guiding vaccine formulation. It examines mechanisms of action across diverse platforms-including mRNA, peptide, and dendritic cell vaccines-and explores synergistic strategies that combine adjuvants or immune checkpoint blockade to enhance efficacy. In addition, we critically evaluate key barriers to success, such as immunosuppressive tumor microenvironments, T-cell dysfunction, and antigenic escape. Finally, we highlight recent clinical advances aimed at overcoming these barriers, thereby outlining a framework for optimizing neoantigen vaccine design to maximize their therapeutic potential in cancer treatment. Notably, encouraging progress has been reported in malignancies such as non-small cell lung cancer and melanoma, underscoring the translational promise of this strategy.

Accurate detection of KRAS codon mutations is essential for precision oncology in colorectal cancer (CRC), yet conventional liquid biopsy methods often lack sufficient sensitivity for rare ctDNA variants, particularly in early diseases. We developed a three-dimensional (3D) plasmonic KRAS microarray integrating blocked recombinase polymerase amplification with plasmon-enhanced fluorescence. Quencher-modified blocking probes suppress wild-type DNA while selectively enabling mutant signal amplification. A single primer-probe set per codon allows comprehensive detection of all substitutions within KRAS codons 12/13, 61, and 146. The platform achieved detection down to 1 fM by direct hybridization and 100 zM after blocked amplification, exceeding conventional PCR and next-generation sequencing sensitivity. Codon-level specificity was validated in CRC cell lines, with distinct signals for each mutation. Clinical analysis of 58 patients showed 100% concordance between tissue, plasma, and urine in mutation-positive malignant cases when sufficient input was available, indicating accurate reflection of tumor profiles. In benign tumors, detection was rare despite tissue mutations, likely due to limited ctDNA release.This plasmonic microarray enables ultra-sensitive, specific, and non-invasive detection, supporting early diagnosis, minimal residual disease monitoring, and longitudinal CRC management.

Prostate, breast, stomach, colon-rectum, lung, and hematologic cancers represent a regional public health burden among older adults in the Caribbean. We described 15-year trends in cancer incidence and mortality among older adults in Martinique. We conducted a population-based cohort study (2008-2022) from the population-based cancer registry of Martinique. Age-Standardized Incidence and Mortality Rates (ASIR and ASMR) were estimated using the Segi/Doll world standard population and Annual Average Percent Change (AAPC) with 95% confidence interval in patients&#x2009;&#x2265;&#x2009;65 years, by tumor site and sex. We recorded 15,400 cancer cases over the entire study period (2008-2022), with 64.4% diagnosed in males. Overall ASIR remained broadly stable: in men, 2,257.8 per 100,000 (95% CI: 2,172.6-2,342.9) in 2008-2012 and 2,053.1 (95% CI: 1,982.8-2,230.4) in 2018-2022; in women, 847.8 (95% CI: 801.8-893.8) in 2008-2012 and 862.1 (95% CI: 821.2-902.9) in 2018-2022. Prostate cancer ASIR decreased from 1,355.5 per 100,000 (95% CI: 1,288.6-1,422.4) in 2008-2012 to 1,303.7 (95% CI: 1,242.0-1,365.5) in 2013-2017, and then significantly to 1,102.2 (95% CI: 1,049.6-1,154.9) in 2018-2022.Prostate cancer ASMR also declined from 293.50 per 100,000 (95% CI: 263.30-323.70) in 2008-2012 to 225.80 (95% CI: 205.00-246.50) in 2018-2022. Women breast cancer ASIR increased significantly from 177.3 per 100,000 (95% CI: 155.4-199.2) in 2008-2012 to 198.0 (95% CI: 176.5-219.6) in 2013-2017 and to 230.7 (95% CI: 208.9-252.5) in 2018-2022. Male lung and bronchial cancer incidence showed a significant AAPC decrease of -12.5% (95% CI: -23.3 to -0.13) in 2018-2022. Colorectal cancer ASMR in women remained stable: 68.2 per 100,000 (95% CI: 55.1-81.3) in 2008-2012, 63.8 (95% CI: 53.0-74.6) in 2013-2017, and 71.4 (95% CI: 60.3-82.5) in 2018-2022, and male stomach cancer AAPC decreased significantly during 2018-2022: -11.5% (95% CI: -20.1 to -1.94). Between 2008 and 2022, cancer incidence among older adults in Martinique showed decreasing prostate and lung cancer but increasing breast cancer, consistent with Caribbean and global trends. These patterns reflect screening practices, treatment advances, and COVID-19 disruptions. Future research should prioritize age-tailored cancer management and uninterrupted treatment access.

Monoclonal antibody-based therapies have substantially improved outcomes in breast cancer, particularly through HER2-directed treatment strategies, but have also introduced important cardiovascular toxicities that require careful recognition and management. This narrative review summarizes current evidence on cardiotoxicity associated with monoclonal antibody therapies used in breast cancer, with emphasis on HER2-targeted antibodies, antibody-drug conjugates, and selected immune checkpoint inhibitors.Trastuzumab remains the best-characterized monoclonal antibody associated with cancer therapy-related cardiac dysfunction, most commonly presenting as left ventricular systolic dysfunction, particularly in patients previously exposed to anthracyclines or with baseline cardiovascular risk factors. Pertuzumab and currently available antibody-drug conjugates have not shown a major increase in cardiotoxic risk beyond that observed with established HER2-directed therapy, although long-term data remain limited for some newer agents. Immune checkpoint inhibitors are less commonly associated with cardiovascular toxicity, but may rarely cause severe immune-mediated complications, particularly myocarditis and also non-immune mediated toxicity such as cardiac dysfunction.Contemporary evaluation of cardiotoxicity increasingly relies on an integrated cardio-oncology framework incorporating left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers, with growing recognition of subclinical dysfunction and right ventricular involvement. Current management strategies emphasize baseline cardiovascular risk assessment, risk-adapted surveillance, early initiation of heart failure therapy when indicated, and individualized multidisciplinary decision-making regarding continuation of anticancer treatment, including permissive cardiotoxicity in selected patients.As the use of monoclonal antibody therapies continues to expand, optimizing the balance between oncologic efficacy and cardiovascular safety remains a central goal of modern breast cancer care.

Multiple myeloma (MM) is best understood as a dynamically evolving genomic ecosystem shaped by inherited susceptibility, early oncogenic events, and continuous selective pressures. We propose an evolutionary genomics framework integrating germline risk, disease initiation, clonal diversification, and therapeutic adaptation into a unified model of MM biology. Polygenic risk burden, rare predisposing variants, and alterations in DNA repair and telomere pathways create a permissive background that influences precursor states and immune interactions. Primary cytogenetic events, particularly immunoglobulin heavy chain (IgH) translocations and hyperdiploidy, establish biologically distinct founding clones and constrain subsequent evolutionary trajectories. Disease progression is driven by secondary chromosomal alterations, copy number changes, MYC activation, TP53 loss, and structural rearrangements, promoting genomic instability and transcriptional plasticity. Longitudinal studies reveal branching clonal architectures shaped by treatment-driven selection. Integrating germline and somatic landscapes within an evolution-aware precision framework may improve risk stratification, anticipate high-risk trajectories, and support adaptive strategies to achieve more durable disease control. While polygenic risk scores (PRS) provide insight into inherited susceptibility, they are not yet clinically actionable for risk stratification or screening in MM and currently remain research tools. This framework provides a clinically oriented basis for applying genomic biomarkers to risk stratification, treatment selection, and longitudinal monitoring.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlapping pathology. Mutations in CCNF, encoding the E3 ubiquitin ligase, Cyclin F, can cause ALS, FTD, or both, even within the same family. Most prior studies of CCNFS621G have relied on overexpression systems, potentially confounding outcomes through disruption of endogenous Cyclin F. Here, we generated the first knock-in mouse model of endogenous CcnfS621G using CRISPR/Cas9. Heterozygous and homozygous CcnfS621G mice showed no motor decline or neuronal loss after 18&#xa0;months, however immunohistochemistry revealed increased hippocampal astrocyte ramification, with sex-, age, and subfield-dependent effects. These data indicate that endogenous CcnfS621G may prime early astrocyte alterations in the absence of overt neurodegeneration. Similar astrocyte morphological changes were observed in canonically affected regions of sporadic ALS and FTD-ALS patients post mortem, as well as in CCNFS621G iPSC-derived astrocytes following inflammatory stimulation. Proteomics on Ccnf mice identified early dysregulation of pathways related to translation, mitochondrial function, cytoskeletal remodelling, synaptic transmission and neuroinflammation. Correspondingly, CCNFS621G iPSC-derived astrocytes displayed impaired mitochondrial membrane potential and altered network morphology under both basal and inflammatory stimuli. As altered neuronal excitability is a hallmark of ALS, we examined astrocyte-driven changes to neuronal excitability. CCNFS621G iPSC-derived motor neurons cultured alone were hyperexcitable, firing more action potentials than isogenic controls. Remarkably, co-culture with CCNFS621G astrocytes, but not isogenic control astrocytes, abolished repetitive firing, increased the proportion of neurons unable to generate action potentials, and reduced voltage-gated sodium currents in CCNFS621G and isogenic control neurons. Together, these findings identify astrocyte alterations as an early feature of CCNFS621G-mediated disease, in the absence of neuronal loss. Moreover, the combination of astrocytic mitochondrial dysfunction and the ability of CCNFS621G astrocytes to suppress repetitive neuronal firing suggests a critical astrocyte-driven non-cell autonomous mechanism that may contribute to an oligogenic role for CCNF in ALS/FTD pathogenesis.

Gold nanoparticles (AuNPs) emerge as promising neuromodulatory biomaterials due to their tunable optical properties, biocompatibility, and ability to cross the blood-brain barrier. Here, we investigated the behavioral and neuroprotective effects of citrate-stabilized AuNPs (~ 19&#xa0;nm) coated with PEG3350 and irradiated under white (AuWL+PEG) or green light (AuGL+PEG), compared with non-irradiated PEGylated AuNPs (AuNP+PEG). Comprehensive physicochemical analyses demonstrated that green-light irradiation enhanced surface plasmon resonance (SPR) activity, improved PEG adsorption, and yielded superior colloidal stability relative to white-light irradiation. In vivo evaluation in Wistar rats revealed that AuGL+PEG produced robust anxiolytic-like effects in the elevated plus maze, significantly enhanced spatial working memory in the Y-maze, and improved performance in the radial arm maze, approaching the efficacy of donepezil. In the forced swimming test, AuGL+PEG also produced the most favorable antidepressant-like profile, reducing immobility without locomotor confounds. Biochemically, AuGL+PEG markedly enhanced antioxidant capacity, increasing SOD, CAT, GPX, and GSH levels while reducing lipid peroxidation (MDA), consistent with restored redox homeostasis. Acetylcholinesterase inhibition was significantly greater in irradiated groups, supporting improved cholinergic signaling. Toxicological evaluation indicated no major systemic or hematological toxicity at the administered doses. Collectively, the findings demonstrate that light-engineered PEGylated AuNPs, particularly those activated with green light, exhibit potent neuroprotective and cognition-enhancing effects mediated by plasmonic surface optimization, antioxidant defense reinforcement, and cholinergic modulation. These results identify AuGL+PEG as a promising candidate nanomaterial for future applications in neuromodulation, cognitive enhancement, and the treatment of neurodegenerative diseases.