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[A preliminary study on molecular target identification of drugs in individualized treatment of malignant solid
1Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Abstract:
Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), β(3)-tubulin (Tubulinβ(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.
Insights
Identifying drug-related molecular targets in children
Area of Science:
- Oncology
- Molecular Biology
- Pediatric Medicine
Background:
- Malignant solid tumors in children present a significant therapeutic challenge.
- Individualized treatment strategies are crucial for improving outcomes.
- Identifying specific drug targets can optimize therapy selection.
Purpose of the Study:
- To investigate the role of identifying drug-related molecular targets in tailoring treatments for pediatric malignant solid tumors.
- To analyze the efficacy and toxicity of various chemotherapy agents based on identified molecular targets.
Main Methods:
- Retrospective analysis of clinical data from 40 pediatric patients with malignant solid tumors.
- Utilized immunohistochemistry, polymerase chain reaction, and sequencing to identify tumor drug molecular targets.
- Compared chemotherapy efficacy and side effect incidence across different molecular targets and tumor types.
Main Results:
- Four key drug-related targets were identified: DNA topoisomerase-ⅡA (TOPOⅡA), Tubulinβ(3), DNA topoisomerase-Ⅰ (TOPOⅠ), and DHFR (C829T) gene polymorphisms.
- Platinum-based agents showed high efficacy (90.0%), followed by methotrexate (85.0%) and irinotecan (70.0%).
- Mesenchymal tumors responded better to irinotecan, methotrexate, and vinblastine compared to non-mesenchymal tumors, while platinum-based drugs were more effective in non-mesenchymal types. Toxic side effects varied, with anthracycline being the most intense.
Conclusions:
- Molecular target identification can predict tumor sensitivity to specific anti-cancer drugs.
- This approach provides a basis for personalized chemotherapy selection in pediatric malignant solid tumors.
- Understanding drug targets and tumor origin aids in optimizing treatment efficacy and minimizing adverse events.
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