New clinical trial design in precision medicine: discovery, development and direction

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to underestimation significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials could provide optimal therapy customization specific biomarkers were developed including basket, umbrella, platform trial designs under master protocol framework. recent years, successive FDA approval indications based on biomarker-guided demonstrated these new clinical ushering tremendous opportunities. Despite rapid increase number current research understanding designs, as compared remains limited. The majority focuses methodologies, there is lack in-depth insight concerning underlying biological logic designs. Therefore, we this comprehensive review discovery development their perspective medicine. Meanwhile, discuss future directions potential design view “Precision Pro”, “Dynamic Precision”, “Intelligent Precision”. This would assist trial-related researchers enhance innovation feasibility by expounding logic, which be essential accelerate progression

Language: Английский

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Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 11, 2024

Novel therapeutic agents in clinical trials offer a paradigm shift the approach to battling this prevalent and destructive disease, area of cancer therapy is on precipice trans formative revolution. Despite importance tried-and-true treatments like surgery, radiation, chemotherapy, disease continues evolve adapt, making new, more potent methods necessary. The field currently witnessing emergence wide range innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, vaccines, utilizes host's immune system selectively target eradicate malignant cells while minimizing harm normal tissue. development targeted medicines kinase inhibitors monoclonal antibodies has allowed for less harmful approaches treating cancer. With help genomics molecular profiling, "precision medicine" customizes therapies each patient's unique genetic makeup maximize efficacy unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, an increasing emphasis combination with synergistic effects further broaden landscape. Multiple-stage are essential determining safety these novel drugs, allowing patients gain access also furthering scientific understanding. future rife promise, as integration artificial intelligence big data potential revolutionize early detection prevention. Collaboration among researchers, healthcare providers, active involvement remain bedrock ongoing battle against In conclusion, dynamic evolving landscape provides hope improved treatment outcomes, emphasizing patient-centered, data-driven, ethically grounded we collectively strive towards cancer-free world.

Language: Английский

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Identification of a novel disulfidptosis-related gene signature in osteoarthritis using bioinformatics analysis and experimental validation

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 8, 2025

Osteoarthritis (OA) is a degenerative bone disease characterized by the destruction of joint cartilage and synovial inflammation, involving intricate immune regulation processes. Disulfidptosis, novel form programmed cell death, has recently been identified; however, effects roles disulfidptosis-related genes (DR-DEGs) in OA remain unclear. We obtained six datasets from GEO database, using four as training sets two validation sets. Differential expression analysis was employed to identify DR-DEGs, unique molecular subtypes were constructed based on these DR-DEGs. Subsequently, microenvironment patients comprehensively analyzed "CIBERSORT" algorithm for infiltration. Various machine learning algorithms utilized screen characteristic nomogram models ROC curves built genes. The scRNA dataset (GSE169454) used classify chondrocytes samples into distinct types, further exploring gene distribution correlation DR-DEGs with specific subpopulations. Moreover, levels validated through rat models. In our study, we identified 10 significant differences within samples. Based recognized (cluster 1 2). ZNF484 NDUFS1 found be significantly overexpressed subtype 1, while infiltration abundance activated mast cells markedly elevated 2. observed proportions 11 types between control samples, 9 demonstrating substantial correlations levels. Further revealed that SLC3A2 NDUFC1 predominantly expressed preHTC subpopulation. All exhibited notably higher EC subpopulation across various types. proportion subgroups high increased, mainly enriching pathways related such IL-17 signaling pathway TGF-beta pathway. Using learning, which, combination models, demonstrated promising performance diagnosis OA. Additionally, vivo confirmed elevation PPM1F This study potential biomarkers classification provided preliminary understanding their role microenvironment. However, experimental clinical studies are required validate diagnostic value therapeutic potential.

Language: Английский

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Trust, Ethics, and User-Centric Design in AI-Integrated Genomics

Published: Feb. 26, 2024

This study examines the integration of genomics and artificial intelligence (AI) in healthcare industry, focusing on ethical trust-related issues that arise from this integration. highlights significance protecting genomic data by employing homomorphic encryption. emphasizes algorithmic transparency. It suggests interpretative frameworks like Local Interpretable Model-agnostic Explanations (LIME) SHapley Additive exPlanations (SHAP) to enhance comprehensibility AI algorithms. The article discusses two key regulatory measures: Trustworthy Artificial Intelligence Initiative Genomic Data Sharing (GDS) Policy. effectiveness current practices adapting rapid technological advancements while maintaining standards. attaining a balance between benefits predictive analytics considerations, such as informed consent integrity, we transition big mechanisms. importance lies its ability revolutionize sector. robust governance ensure adhere standards earn public trust. In summary, it is imperative acknowledge address considerations associated with integrating effective responsible implementation. area major focus contemporary medical research practice.

Language: Английский

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Applications and advances in molecular diagnostics: revolutionizing non-tuberculous mycobacteria species and subspecies identification

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: June 19, 2024

Non-tuberculous mycobacteria (NTM) infections pose a significant public health challenge worldwide, affecting individuals across wide spectrum of immune statuses. Recent epidemiological studies indicate rising incidence rates in both immunocompromised and immunocompetent populations, underscoring the need for enhanced diagnostic therapeutic approaches. NTM often present with symptoms similar to those tuberculosis, yet less specificity, increasing risk misdiagnosis potentially adverse outcomes patients. Consequently, rapid accurate identification pathogen is crucial precise diagnosis treatment. Traditional detection methods, notably microbiological culture, are hampered by lengthy incubation periods limited capacity differentiate closely related subtypes, thereby delaying initiation targeted therapies. Emerging technologies offer new possibilities swift infections, playing critical role early providing more comprehensive information. This review delineates current molecular methodologies species subspecies identification. We critically assess limitations challenges inherent these diagnosing explore potential future directions their advancement. It aims provide valuable insights into advancing application techniques infection

Language: Английский

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Research Trends and Development Dynamics of qPCR-based Biomarkers: A Comprehensive Bibliometric Analysis

Molecular Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

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Exploring the connection between RNA splicing and intellectual disability

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 91, P. 102322 - 102322

Published: Feb. 8, 2025

Intellectual disability (ID) is a broad diagnostic category that encompasses individuals with impaired cognitive ability. While these disorders have heterogeneous causes, recent developments in next-generation sequencing (NGS) are revealing the prevalence of genetic etiologies. In particular, germline mutations genes affect RNA splicing increasingly common causes ID disorders. Research to elucidate functional relationship between and neurodevelopment critical since molecular therapeutics require nuanced understanding pathological mechanism. this review, we first summarize trends led discovery splicing-ID relationship, then discuss progress future directions for research surrounding neurodevelopment. Finally, speak on how results may serve as foundation burgeoning therapies.

Language: Английский

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Advances in next-generation sequencing (NGS) applications in drug discovery and development

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Drug discovery is a complex and multifaceted process driven by scientific innovation advanced technologies. Next-Generation Sequencing (NGS) platforms, encompassing both short-read long-read technologies, have revolutionized the field enabling high-throughput cost-effective analysis of DNA RNA molecules. Continuous advancements in NGS-based technologies enabled their seamless integration across preclinical clinical workflows drug discovery, early-stage target identification, candidate selection, genetically stratified trials, pharmacogenetic studies. This review provides an overview current potential applications development process, including roles novel screening, medication The based on literature retrieval from PubMed Web Science databases between 2018 2024. As advance rapidly, NGS enhances accuracy generates vast datasets. These datasets are extensively integrated with other heterogeneous data systems biology mined using machine learning to extract significant insights, thereby driving progress discovery.

Language: Английский

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Advancing chronic myeloid leukemia research with next-generation sequencing: potential benefits, limitations, and future clinical integration

Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Language: Английский

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Hypotheses of development and strategies for overcoming drug resistance in epilepsy. Рart II: Overcoming strategies

Epilepsy and Paroxysmal Conditions, Journal Year: 2025, Volume and Issue: 17(1), P. 59 - 70

Published: May 2, 2025

To date, despite the complexity and risks of not removing seizures hippocampal resection is only effective solution to overcome drug resistance in epilepsy. Recently, a significant amount data has been accumulated on mechanisms development, which allows develop innovative strategies it. New antiepileptic drugs have emerging, directly aimed at acting disease etiological substrate (many them are stage clinical trials). Targeted therapy extensively introduced, coupled with precision medicine methods can potentially aid finding personalized approach each individual patient. Migraine models also achieve qualitatively new level, providing researchers an opportunity highly systems for identifying previously unknown components, as well assessing effect drugs. The aim this review was highlight current approaches treatment epilepsy overcoming resistance.

Language: Английский

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