With the rapid advancements in cancer treatment, targeted therapies have increasingly become a significant approach in precision medicine. However, the cardiac toxicity associated with these targeted leads has raised considerable concern and poses a substantial challenge. To address this issue, Creative Biolabs offers specialized services for targeted drug development and cardiac toxicity assessment, supporting every stage of the drug development process.

Introduction

In the current wave of modern cancer research, the development of targeted therapies is emerging as a significant breakthrough. These targeted drugs specifically attack cancer cells, greatly enhancing the effectiveness and precision of the treatment. However, as the use of targeted therapies becomes more widespread, issues such as cardiotoxicity have begun to surface, posing new challenges to drug safety.

As a result, Creative Biolabs is dedicated to assessing cardiotoxicity during the development of targeted therapies, offering comprehensive safety analysis services. We can systematically evaluate the effects of targeted drugs on the heart through electrocardiogram monitoring, cardiac function assessment, and biomarker analysis. By choosing our CRO services, you can not only expedite the development of targeted therapies but also ensure the scientific rigor and safety of your research.

Fig.1 Mechanism of Cardiac Toxicity with Different Anticancer Agents.^1,3

Services

The development of targeted therapies represents a significant advancement in the field of modern drug research. These therapies work by identifying and interacting with specific molecular targets, allowing for more precise treatments for cancer and various other conditions. However, despite their demonstrated efficacy, targeted drugs can also lead to a range of cardiotoxic side effects. This highlights the crucial need for Creative Biolabs to establish a technical platform for analyzing the cardiotoxicity associated with these targeted therapies.

In our labs, the process begins with drug screening, after which we assess cell viability and cardiac function using cellular models such as cardiac cell lines or induced pluripotent stem cell-derived cardiomyocytes. Next, we employ electrophysiological techniques to examine the effects of drugs on cardiac electrical activity, including their negative chronotropic effects and the incidence of arrhythmias. Moreover, through long-term observations using animal models, we assist clients in monitoring the potential impacts of drugs on cardiac structure and function, utilizing a combination of echocardiographic imaging and electrocardiographic monitoring to provide a comprehensive evaluation of cardiac toxicity.

• Targeted Drug Development: Offer comprehensive guidance throughout the entire process of targeted drug development, including target selection, drug design, and optimization.
• Cardiotoxicity Evaluation: Employ advanced technological methods for screening and assessing the cardiotoxicity of drugs, utilizing cellular models, animal studies, and preclinical research.
• Data Analysis and Interpretation: Provide thorough data analysis reports, integrating bioinformatics tools to assist clients in accurately comprehending the mechanisms of cardiotoxicity.

Fig.2 Shows the Coverage of Proteomic, Epigenomic, and Transcriptomic Data.^2,3

Case Study: Development of Targeted Drug X and Its Associated Cardiotoxicity Analysis

• Background

Targeted drug X is a novel small molecule designed to target specific surface markers on cancer cells, to enhance the selectivity and efficacy of tumor treatment. To evaluate its safety, particularly regarding cardiotoxicity, we have conducted a series of experiments.

• Experimental Process

1. Drug Screening and Optimization
   - Initially, dozens of compounds were screened, ultimately identifying XYZ as a leading candidate.
   - In vitro studies were performed using human tumor cell lines (such as MCF-7 and A549) to assess the drug's activity, monitoring the rate of cell proliferation inhibition.
2. Animal Studies
   - Eight-week-old SD rats were randomly assigned to a control group and a treatment group (receiving XYZ at a dose of 10 mg/kg).
   - After four weeks of administration, changes in body weight and behavioral status of the animals were monitored.
3. Cardiac Function Assessment
   - Echocardiograms were employed to evaluate cardiac function in the rats, focusing on ejection fraction (EF) as well as ventricular systolic and diastolic function.
   - Cardiac tissues were collected for histological analysis to observe any pathological changes.
4. Biochemical Analysis
   - Cardiac-specific biomarkers (such as troponin I and BNP) in the blood were quantified using ELISA methods.
5. Electrocardiogram (ECG) Monitoring
   - A 24-hour dynamic ECG was conducted both before and following treatment to assess potential arrhythmias.

• Key Findings

1. Cellular Experiment Results
   - The IC50 value for X against MCF-7 cells was found to be 0.6 μM, while for A549 cells it was 1.3 μM, indicating strong anti-tumor activity.
2. Animal Experiment Results
   - Two weeks post-treatment, a weight reduction of 5% was observed in the drug group rats, while the control group showed no significant changes.
   - Echocardiography indicated that the ejection fraction (EF) in the drug group rats decreased from a baseline of 75% to 63%, suggesting impaired cardiac function.
3. Biochemical Analysis Results
   - The levels of cardiac troponin I in the drug group rats significantly increased from a normal value of 0.05 ng/mL to 0.1 ng/mL, while BNP levels rose from a normal range of 20 pg/mL to 50 pg/mL.
4. Electrocardiogram Results
   - Continuous ECG monitoring revealed that the drug group rats experienced episodes of transient arrhythmia, characterized by sinus tachycardia with a maximum heart rate reaching 220 bpm.

As targeted therapies become more widely used, concerns about cardiac toxicity are increasingly coming to the forefront. Our cardiac toxicity analysis service is dedicated to evaluating the potential effects of targeted drugs on the heart. We utilize cutting-edge experimental techniques and data analysis methods to provide in-depth insights into the mechanisms of drug action. Whether you are just starting your journey in targeted drug development or evaluating cardiotoxicity, Creative Biolabs is ready to offer you our expert assistance. Don't hesitate to contact us at any time.

References

1. El-Cheikh, Jean, et al. "Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies." Blood Cancer Journal 13.1 (2023): 83.
2. Verheijen, Marcha, et al. "Multi-omics HeCaToS dataset of repeated dose toxicity for cardiotoxic & hepatotoxic compounds." Scientific data 9.1 (2022): 699.
3. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use