DrugCombo:一种针对抗癌药物组合的信息桥梁,用于I期试验设计
Lei Wang1, Shijun Zhang1, Lai Wei1,2
1Department of Biomedical Informatics, The Ohio State University College of Medicine, 1800 Cannon Drive Columbus, OH 43210, United States.
Database : the journal of biological databases and curation
|September 25, 2025
概括
DrugCombo是一个新的知识库,整合了癌症药物毒性数据. 该资源有助于设计I期临床试验,提供关于最大可容忍剂量和剂量限制毒性的关键信息,旨在减少试验失败.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 生物信息学是一种生物信息学.
背景情况:
- 对癌症的组合药物治疗有希望,但面临着高的第一阶段试验失败率.
- 一个主要的挑战是缺乏针对癌症药物的综合毒性数据.
- 这阻碍了临床医生和生物统计学家的有效试验设计.
研究的目的:
- 开发DrugCombo,这是针对癌症药物的综合药物毒性数据的全面知识库.
- 通过提供重要的毒性信息,促进I期临床试验的设计.
- 为了提高组合癌症药物治疗的成功率.
主要方法:
- 来自多个来源的综合药物毒性数据,包括药物标签和PubMed.
- 使用了微软研究的双向编码器,从生物医学文本挖掘转换器 (MSR BiomedBERT) 来进行数据提取.
- 包括数据,如最大可容忍剂量 (MTD),剂量限制毒性 (DLT),剂量范围和药理学相互作用.
主要成果:
- DrugCombo集成了DrugBank,药物标签,FDA不良事件报告系统和I期试验的数据.
- 包含来自2592项试验的8,797种药物相互作用,3,995种严重的ADE,95,535种常见的ADE,1,816,030种ADE和MTD/DLT.
- 对阿克西替尼和尼沃卢马布试验的回顾性分析强调了由于忽视的毒性重叠而导致初始剂量选择的潜在问题.
结论:
- DrugCombo是第一个为I期试验设计提供集成MTD,DLT和剂量范围数据的数据库.
- 该资源有助于研究人员选择适当的起始剂量和范围.
- 这些全面的毒性数据旨在提高未来癌症临床试验的成功率.
相关概念视频
Combination Therapies and Personalized Medicine
5.8K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.8K
Clinical Trials: Overview
4.5K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.5K
Drug Discovery: Overview
10.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.9K
Hazard Ratio
543
The hazard ratio (HR) is a widely used measure in clinical trials to compare the risk of events, such as death or disease recurrence, between two groups over time. It reflects the ratio of hazard rates—the instantaneous risk of the event occurring—between a treatment group and a control group. This measure provides valuable insights into the relative effectiveness of a treatment by assessing how the risk of an event differs between the two groups.
For example, in a clinical trial...
For example, in a clinical trial...
543
Dosage Regimens: Designs and Approaches
227
Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
227
Drug Administration and Therapy Phases: Overview
1.1K
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
1.1K


