Paclitaxel Anti-Tumor: Mechanism, Model Optimization and Drug Resistance Response

Abstract

Paclitaxel (PTX) is a first-line anti-cancer chemotherapy agent. Its core mechanism of action is to specifically bind to tubulin, inhibit microtubule depolymerization, stabilize microtubule structure, and ultimately induce apoptosis. It is widely used in the treatment of breast, ovarian, and gastric cancers. However, PTX suffers from poor water solubility, low oral bioavailability, and reliance on the toxic excipient Cremophor EL, which can cause allergic reactions. Long-term use can easily lead to drug resistance, severely limiting its clinical application. To overcome these bottlenecks, this paper analyzes research on PTX dosage forms and drug resistance, and find that dosage form optimization is crucial. Marketed nanoformulations, such as liposomes (Lipusu®), albumin nanoparticles (Abraxane®), and polymeric micelles (Genexol®-PM), significantly reduce toxic side effects and enhance efficacy by improving solubility, enhancing tumor targeting (via the EPR effect or active modification), and avoiding toxic excipients. To address drug resistance, research is underway to effectively reverse or delay the onset of drug resistance by inhibiting cancer stem cell (CSC) stemness and vascular mimicry (VM), as well as suppressing the expression of drug resistance genes. In the future, research on PTX can focus on its effectiveness and safety, continuously optimize the preparation process, and develop more efficient and safer PTX preparations.