Tubulin and Deoxyribonucleic acid (DNA)

This target entry refers to the synergistic pharmacological interaction between paclitaxel-stabilized microtubules and cisplatin-induced DNA adducts, rather than a single molecular entity. Paclitaxel is a microtubule-stabilizing agent that binds to the beta-subunit of tubulin, interfering with the transition from metaphase to anaphase and inducing cell cycle arrest at the G2/M phase (Jordan & Wilson, 2004). Cisplatin is a platinum-based compound that forms covalent intra-strand and inter-strand cross-links with DNA, which obstructs DNA replication and transcription, leading to programmed cell death (Dasari & Bernard, 2014). The combination of these two mechanisms is widely utilized in oncology, particularly for treating ovarian and lung cancers, where they exhibit sequence-dependent synergy. Clinical studies have shown that administering paclitaxel before cisplatin maximizes efficacy, whereas the reverse sequence can lead to increased toxicity due to cisplatin-induced reduction in paclitaxel clearance (Rowinsky et al., 1991). This dual-targeting approach aims to overwhelm cellular repair mechanisms and bypass drug resistance, though it is associated with significant side effects such as peripheral neuropathy and myelosuppression.

Other names

Combined cytotoxic interaction: paclitaxel-stabilized microtubules and cisplatin-DNA adductsPaclitaxel-Cisplatin combinationTaxol-Cisplatin synergyMicrotubule-DNA adduct interaction

Paclitaxel stabilizes microtubules to induce mitotic arrest, while cisplatin forms DNA adducts to inhibit replication; their combination synergistically promotes apoptosis.