Integrated Biomolecular Profiling and Mechanism Evaluation (IBProME) as an Explanatory Approach to Trabectedin's Anticancer Activity
DOI:
https://doi.org/10.48402/IMIST.PRSM/jasab-v7i2.58180Keywords:
Trabectedin, Cancer, Drug Mechanism, ABCB1 (P-glycoprotein), IBProMEAbstract
This article presents the Integrated Bioinformatics and Molecular Profiling for Drug Evaluation (IBProME) method, applied to analyze the anticancer activity of Trabectedin, a molecule derived from marine sources. Selected for clinical development due to its unique chemical structure and efficacy against various cancers, including soft tissue sarcomas and ovarian cancer, Trabectedin stands out for its distinct mechanism of action. It inhibits activated transcription, disrupting DNA repair and causing DNA double-strand breaks. This leads to the degradation of RNA polymerase II, a key enzyme for gene transcription. Notably, this process is especially effective in tumor cells deficient in DNA repair, such as those with mutations in the BRCA1 and BRCA2 genes. Additionally, Trabectedin impacts the tumor microenvironment by reducing mononuclear macrophages and inhibiting angiogenesis, which is crucial for the formation of new blood vessels. The IBProME approach integrates quantum chemistry, in silico toxicology, and molecular modeling techniques, enabling the prediction of Trabectedin's biological and toxicological effects prior to clinical trials. A key aspect of this study is the examination of the ABCB1 protein complex (P-glycoprotein, or MDR1), which plays a significant role in anticancer drug resistance. The structural data obtained provide valuable insights into the interactions between ABCB1 and inhibitors, offering a foundation for developing more targeted treatments against drug resistance.
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