The article discusses the mechanism of action of Taxol (paclitaxel), a microtubule-stabilizing drug used to treat various cancers. Initially, Taxol was discovered from the Pacific yew tree through a collaboration between the National Cancer Institute and the U.S. Department of Agriculture. Despite initial challenges, Taxol entered clinical trials and showed promise in treating ovarian, breast, and lung cancers. However, the limited supply and environmental concerns led to the development of paclitaxel, which is now widely used. Paclitaxel's primary mechanism of action involves stabilizing microtubules, leading to mitotic arrest and cell death. However, recent studies have revealed that intratumoral concentrations of paclitaxel are often too low to cause mitotic arrest, instead leading to multipolar divisions. This insight suggests that the cytotoxic effect of paclitaxel may be due to chromosome missegregation on multipolar spindles rather than mitotic arrest. The article also highlights the challenges in studying the mechanism of paclitaxel, including the difficulty in determining intratumoral concentrations and the stochastic nature of cell fate after mitotic arrest. Additionally, it discusses the implications of these findings for the development of biomarkers to predict patient response to paclitaxel therapy and the potential for new drugs targeting mitotic arrest without affecting microtubule dynamics. In conclusion, the article emphasizes the importance of understanding the clinically relevant mechanism of paclitaxel to improve its therapeutic efficacy and develop more effective treatments for cancer.The article discusses the mechanism of action of Taxol (paclitaxel), a microtubule-stabilizing drug used to treat various cancers. Initially, Taxol was discovered from the Pacific yew tree through a collaboration between the National Cancer Institute and the U.S. Department of Agriculture. Despite initial challenges, Taxol entered clinical trials and showed promise in treating ovarian, breast, and lung cancers. However, the limited supply and environmental concerns led to the development of paclitaxel, which is now widely used. Paclitaxel's primary mechanism of action involves stabilizing microtubules, leading to mitotic arrest and cell death. However, recent studies have revealed that intratumoral concentrations of paclitaxel are often too low to cause mitotic arrest, instead leading to multipolar divisions. This insight suggests that the cytotoxic effect of paclitaxel may be due to chromosome missegregation on multipolar spindles rather than mitotic arrest. The article also highlights the challenges in studying the mechanism of paclitaxel, including the difficulty in determining intratumoral concentrations and the stochastic nature of cell fate after mitotic arrest. Additionally, it discusses the implications of these findings for the development of biomarkers to predict patient response to paclitaxel therapy and the potential for new drugs targeting mitotic arrest without affecting microtubule dynamics. In conclusion, the article emphasizes the importance of understanding the clinically relevant mechanism of paclitaxel to improve its therapeutic efficacy and develop more effective treatments for cancer.