Cancer nuclear envelope rupture and repair in taxane resistance

Taxanes, including paclitaxel, docetaxel, and cabazitaxel, are key agents in cancer treatment, often used as front-line chemotherapy drugs in combination with other agent(s) (commonly carboplatin) and as second-line treatments alone. Generally, taxanes are highly effective, but drug resistance unavoidably develops following repeated treatment. Taxanes work by binding to and stabilizing microtubules, leading to mitotic arrest, mitotic catastrophe, and micronucleation. The long-recognized mechanisms of drug resistance generally can be classified into three categories: drug efflux, microtubule polymerization, and apoptotic pathway. A recent new addition to this list is a mechanism related to the nuclear envelope, as cancer cells undergo micronucleation and nuclear membrane rupture when treated with taxanes. All these mechanisms may operate simultaneously as taxane resistance is multi-factorial. Here, we review the cell biology understanding of nuclear envelope breaking in production of micronucleation, and nuclear membrane rupture and repair, and propose that these processes are involved in taxane resistance.