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Review
. 2024 Jul 13;24(1):244.
doi: 10.1186/s12935-024-03415-0.

Key genes and molecular mechanisms related to Paclitaxel Resistance

Adel I Alalawy  1
Affiliations
Review

Key genes and molecular mechanisms related to Paclitaxel Resistance

Adel I Alalawy. Cancer Cell Int. .

Abstract

Paclitaxel is commonly used to treat breast, ovarian, lung, esophageal, gastric, pancreatic cancer, and neck cancer cells. Cancer recurrence is observed in patients treated with paclitaxel due to paclitaxel resistance emergence. Resistant mechanisms are observed in cancer cells treated with paclitaxel, docetaxel, and cabazitaxel including changes in the target molecule β-tubulin of mitosis, molecular mechanisms that activate efflux drug out of the cells, and alterations in regulatory proteins of apoptosis. This review discusses new molecular mechanisms of taxane resistance, such as overexpression of genes like the multidrug resistance genes and EDIL3, ABCB1, MRP1, and TRAG-3/CSAG2 genes. Moreover, significant lncRNAs are detected in paclitaxel resistance, such as lncRNA H19 and cross-resistance between taxanes. This review contributed to discovering new treatment strategies for taxane resistance and increasing the responsiveness of cancer cells toward chemotherapeutic drugs.

Keywords: ABCB1; Paclitaxel; Resistance; TRAG-3/CSAG2 gene.

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1
Chemical structure of paclitaxel
Fig. 2
Fig. 2
Mechanisms of paclitaxel mode of actions. (A) Paclitaxel targets 𝛽-tubulin heterodimers and stabilizes microtubule dynamics to prevent cell proliferation. (B) Paclitaxel causes microtubule depolymerization and arresting cells, especially in the G2/M phase and finally undergoing apoptosis. (C) Paclitaxel downregulates the expression level of bcl2 and drives the efflux of the mitochondrial cytochrome c resulting in caspase activation
Fig. 3
Fig. 3
(A) Chemical structure of docetaxel. (B) Mode of action of docetaxel; docetaxel binds to β-tubulin causing the distribution of microtubules resulting arrest of cancer cells at the G2/M phase. Furthermore, it triggers apoptosis by causing disturbance in mitochondrial dynamics and drives the release of cytochrome c and upregulating BAX levels. Docetaxel Raf-1 kinase phosphorylates Bcl-2 resulting in apoptosis
Fig. 4
Fig. 4
Chemical structure of cabazitaxel
Fig. 5
Fig. 5
Resistant mechanisms of paclitaxel
Fig. 6
Fig. 6
Key genes related to paclitaxel resistance
Fig. 7
Fig. 7
MiR-1273 g-3p, miR-34a, miR-135b, miR-34a-5p, miR-155, miR-24–3p, induces paclitaxel and docetaxel resistance, on the other hand, miR-148, and miR-200 restore the sensitivity of resistant cancer cells
See this image and copyright information in PMC

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