Available online 15 October 2022, 100881
ABSTRACTTaxanes (Taxol/paclitaxel, Docetaxel/taxotere) are a key group of successful drugs commonly used in chemotherapy to treat several major malignant tumors also as a front-line agent in combination with carboplatin/cisplatin, as well as a second line drug with a dose dense regimen following recurrence. Overall, the response to paclitaxel is excellent, though drug resistance inevitably develops in subsequent treatments. The commonly accepted mechanism of action is that the hindrance of microtubule function by paclitaxel leads to cell cycle arrest at mitosis, and subsequent apoptosis. The mechanisms for resistance to paclitaxel have also been extensively investigated, such as ABC transporter overexpression, altered signaling and apoptotic gene expression to resist cell death, and changes associated with microtubules to reduce influences of the drugs. Meanwhile, another important mechanism of paclitaxel resistance has been proposed: increased nuclear lamina/envelope sturdiness to retard the breaking of nuclear envelop and the paclitaxel-induced multinucleation as well as the formation of multiple micronuclei. Here in this review, we focus on experimental findings and ideas on the mechanism of paclitaxel resistance related to cancer nuclear envelope, to provide new insights on overcoming paclitaxel resistance.
AbbreviationscGASCyclic GMP-AMP synthase
LINCLinker of Nucleoskeleton and Cytoskeleton
PAP stainingPapanicolaou stain
Stingstimulator of interferon genes
KeywordsPaclitaxel
drug resistance
Lamin A/C
nuclear envelope
nuclear fragmentations
nuclear envelope malleability
micronuclei
nuclear lamina
microtubule
mitotic inhibitor
ovarian cancer
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