Association of genetically proxied cancer-targeted drugs with cardiovascular diseases through Mendelian randomization analysis

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 6, 2025

Cancer-targeted therapies are progressively pivotal in oncological care. Observational studies underscore the emergence of cancer therapy-related cardiovascular toxicity (CTR-CVT), impacting patient outcomes. We aimed to investigate causal relationship between different types cancer-targeted and disease (CVD) outcomes through a two-sample Mendelian randomization (MR) study. This genome-wide association study was conducted using framework. Genetic instruments for drug target gene expression were extracted from eQTLGen consortium (31684 individuals, 37 cohorts). Genome-wide (GWAS) summary statistics 19 diseases derived FinnGen database. Primary analysis carried out summary-data-based MR (SMR) method, with sensitivity validation. Colocalization identifies shared variants exposure eQTLs CVD-associated single-nucleotide polymorphisms (SNPs). Among 39 genes, 8 identified detectable cis-eQTLs subsequently validated positive control further investigation. In SMR analyses, genetically proxied VEGFA inhibition showed significantly strong stroke (odds ratio [OR] = 1.17, 95% confidence interval [CI] 1.09–1.26, p 1.33 × 10− 5). Additionally, FGFR1, FLT1, MAP2K2 exhibited suggestive corresponding Nevertheless, only variant (93.6%), whereas MAP2K2, FLT1 did not share colocalization analysis. genetic revealed evidence supporting use inhibitors increased risk, highlighting need enhanced pharmacovigilance. These findings delicate balance risk benefits therapy.

Язык: Английский

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Genetic factors in the pathogenesis of cardio-oncology

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Авг. 5, 2024

In recent years, with advancements in medicine, the survival period of patients tumours has significantly increased. The adverse effects tumour treatment on patients, especially cardiac toxicity, have become increasingly prominent. elderly breast cancer, treatment-related cardiovascular toxicity surpassed cancer itself as leading cause death. Moreover, an increasing number novel antitumour drugs, such multitargeted agents, antibody‒drug conjugates (ADCs), and immunotherapies, been applied clinical practice. cardiotoxicity induced by these drugs more pronounced, to a complex diverse mechanism damage. risks unintended are increased high-dose anthracyclines, concurrent radiation, addition traditional risk factors smoking, hypertension, diabetes, hyperlipidaemia, obesity. However, do not fully explain why only subset individuals experience whereas others similar features not. Recent studies indicate that genetics play significant role susceptibility development from therapies. These genes involved drug metabolism, oxidative damage, dysfunction, other processes. emerging evidence suggests epigenetics also plays drug-induced toxicity. We conducted review focusing example help oncologists cardiologists better understand mechanisms genetic this review, we specifically address relationship between alterations including chemotherapy-related changes, targeted therapy-related immune changes. discuss epigenetic hope will improve stratification enable therapeutic interventions mitigate consequences life-saving treatments.

Язык: Английский

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Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 26, 2025

Abstract The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in treatment recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone tumor immunotherapy, have emerged as one most promising advancements treatment. Although ICIs, such CTLA-4 PD-1/PD-L1 inhibitors, demonstrated clinical efficacy, their therapeutic impact remains suboptimal due patient-specific variability immune resistance. Cell death is fundamental process for maintaining tissue homeostasis function. Recent research highlights that combination induced regulatory cell (RCD) ICIs can substantially enhance anti-tumor responses across multiple types. In cells exhibiting high levels recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers programmed (PCD) pathway characterized disulfide bond formation REDOX (reduction-oxidation) reactions, termed “disulfidptosis.” Studies suggest disulfidptosis plays critical role efficacy SLC7A11 cancers. Therefore, investigate potential synergy between this study will explore mechanisms both processes progression, with goal enhancing response targeting intracellular pathway.

Язык: Английский

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The Cardiotoxicity Risk of Immune Checkpoint Inhibitors Compared with Chemotherapy: A Systematic Review and Meta-analysis of Observational Studies

Cardiovascular Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Язык: Английский

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Updates in Diagnosis and Treatment of Immune Checkpoint Inhibitor Myocarditis

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Апрель 3, 2025

Язык: Английский

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Interaction between post-tumor inflammation and vascular smooth muscle cell dysfunction in sepsis-induced cardiomyopathy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Sepsis-induced cardiomyopathy (SIC) presents a critical complication in cancer patients, contributing notably to heart failure and elevated mortality rates. While its clinical relevance is well-documented, the intricate molecular mechanisms that link sepsis, tumor-driven inflammation, cardiac dysfunction remain inadequately explored. This study aims elucidate interaction between post-tumor intratumor heterogeneity, of VSMC SIC, as well evaluate therapeutic potential exercise training specific pharmacological interventions. Transcriptomic data from NCBI GEO databases were analyzed identify differentially expressed genes (DEGs) associated with SIC. Weighted gene co-expression network analysis (WGCNA), ontology (GO), KEGG pathway enrichment analyses utilized biological significance these genes. Molecular docking dynamics simulations used investigate drug-target interactions, immune infiltration mutation carried out by means platforms like TIMER 2.0 DepMap comprehend influence DVL1 on responsiveness. Through utilization datasets, we discovered core exhibited remarkable up-regulated expression both SIC diverse kinds cancers, which poor prognosis inflammatory responses. revealed Digoxin could bind reduce oxidative stress The module related was identified WGCNA, demonstrated distinctive cell patterns impact immunotherapeutic resistance. regulator other cancers and, therefore, can serve target. present suggests targeted therapies enhance response regimens may be novel tool during particularly patients. drugs, Digoxin, require further vivo studies confirm their effects efforts improve outcomes immunotherapy-resistant

Язык: Английский

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Cancer chemoprevention: signaling pathways and strategic approaches

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Апрель 17, 2025

Abstract Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from invasion or recurrence, only over ten drugs approved by the U.S. Food and Drug Administration. Therefore, screening potent is crucial reduce constantly increasing incidence mortality rate of cancer. Considering lengthy prevention process, an ideal agent should be nontoxic, inexpensive, oral. Natural compounds become a natural treasure reservoir for chemoprevention because their superior ease availability, cost-effectiveness, safety. The benefits as in various studies. In light this, present review intended fully delineate entire scope chemoprevention, primarily focuses on aspects based compounds, specifically focusing mechanism action prevention, discussing detail how they exert effects affecting classical signaling pathways, immune checkpoints, gut microbiome. We also introduce novel strategies summarize role improving chemotherapy regimens. Furthermore, we describe discovering anticancer with low abundance high activity, revealing broad prospects drug discovery chemoprevention. Moreover, associate precision medicine, discuss challenges encountered Finally, emphasize transformative potential advancing field ability more effective less toxic preventive options oncology.

Язык: Английский

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Comprehensive macro and micro views on immune cells in ischemic heart disease

Cell Proliferation, Год журнала: 2024, Номер 57(12)

Опубликована: Авг. 1, 2024

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage failure. As complex pathologic condition, it involves intricate regulatory processes at cellular molecular levels. The immune system are closely interconnected, with cells playing crucial role maintaining cardiac health influencing progression. Consequently, alterations microenvironment influenced controlled by various cells, such as macrophages, neutrophils, dendritic eosinophils, T-lymphocytes, along cytokines they produce. Furthermore, studies have revealed Gata6

Язык: Английский

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Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Июнь 10, 2024

Objective Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between atherogenic index of plasma (AIP) and 30-day mortality rate patients with acute decompensated heart failure (ADHF). Methods A total 1,248 ADHF recruited from Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort 2019 2022 were selected for this study. The outcome was rate. Multivariable Cox regression, restricted cubic splines (RCS), stratified analyses utilized assess relationship AIP patients. Mediation models employed exploratory analysis roles inflammation, oxidative stress, nutrition association Results During follow-up, 42 (3.37%) died. rates corresponding quartiles as follows: Q1: 1.28%, Q2: 2.88%, Q3: Q4: 6.41%. multivariable regression revealed positive high [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08–14.28], independent age, gender, type, cardiac function classification, comorbidities. It important note that there U-shaped curve (<0.24) before fourth quartile, lowest risk around an -0.1. Furthermore, mediation suggested significant mediating effects inflammation on related AIP, accounting approximately 24.29% about 8.16% effect. Conclusion retrospective reveals first time According our findings, maintaining -0.1 could be crucial improving poor prognoses medical perspective. Additionally, it and, if necessary, enhance nutritional support anti-inflammatory treatment.

Язык: Английский

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A bibliometric analysis of immunotherapy for atherosclerosis: trends and hotspots prediction

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 19, 2024

An increasing number of studies have demonstrated that immunotherapy may play a significant role in treating Atherosclerosis and has emerged as promising therapy this field. The aim study is to provide comprehensive perspective through bibliometric analysis investigate the existing hotspots frontiers.

Язык: Английский

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