DNA topoisomerases are essential enzymes that regulate DNA topology during replication, transcription, recombination, and chromosomal segregation. Their pivotal role in maintaining genomic stability makes them critical molecular targets in cancer therapy. However, conventional topoisomerase inhibitors face limitations such as drug resistance, off-target toxicity, and variable therapeutic efficacy across tumor types. This review presents a systems biology-based framework for DNA topoisomerase-targeted drug design, integrating molecular structural insights, network-level cellular interactions, and computational modeling approaches to improve therapeutic precision in oncology. By synthesizing evidence from structural enzymology, genomic instability mechanisms, and pharmacological studies, the article highlights how multi-scale biological modeling can enhance drug discovery pipelines. Special emphasis is placed on the mechanistic reconstitution and functional modularity of human topoisomerase I, which provides a foundational basis for rational drug targeting (Stewart et al., 1997). The review further explores clinical implications, including optimization of chemotherapy regimens, reduction of drug resistance, and enhancement of blood-brain barrier penetration strategies in pediatric oncology. The integration of systems-level approaches is shown to offer a transformative pathway for next-generation anticancer therapeutics.
A Systems Biology Approach to DNA Topoisomerase-Targeted Drug Design and Its Clinical Implications in Oncology Treatment Regimens
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References
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