Paclitaxel Resistance Related to Nuclear Envelope Structural SturdinessRunning Title: Lamin A/C Expression and Paclitaxel Resistance

Elsevier

Available online 15 October 2022, 100881

Drug Resistance UpdatesABSTRACT

Taxanes (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.

AbbreviationscGAS

Cyclic GMP-AMP synthase

LINC

Linker of Nucleoskeleton and Cytoskeleton

PAP staining

Papanicolaou stain

Sting

stimulator of interferon genes

Keywords

Paclitaxel

drug resistance

Lamin A/C

nuclear envelope

nuclear fragmentations

nuclear envelope malleability

micronuclei

nuclear lamina

microtubule

mitotic inhibitor

ovarian cancer

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© 2022 Published by Elsevier Ltd.

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