Recent advances in the treatment of advanced prostate cancer: maximizing existing therapies while searching for novel solutions

Gourdin, Theodore Stewart

doi:10.1097/cco.0000000000000822

Cited by 1 publication

(1 citation statement)

References 34 publications

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“…Typically, most advanced PCa patients are initially treated with androgen deprivation therapy; however, most of them develop resistance and progress to castration-resistant prostate cancer (CRPC) [ 3 ]. At this stage, despite the continued development of new therapies, docetaxel (DCT) remains the approved choice due to its efficacy in prolonging lifespan [ 2 , 4 , 5 ]. Unfortunately, the efficacy of DCT treatment is also weakened by the development of resistance and cross-resistance phenomena [ 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Secreted miR-210-3p, miR-183-5p and miR-96-5p reduce sensitivity to docetaxel in prostate cancer cells

Canovai,

Evangelista,

Mercatanti

et al. 2023

Cell Death Discov.

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Docetaxel (DCT) resistance is one of the main factors responsible for treatment failure in metastatic prostate cancer (PCa). Although several mechanisms of DCT resistance have been elucidated, the issue is still far from comprehensive. In this work we show that miR-96-5p, miR-183-5p and miR-210-3p (referred to as sDCTR-miRNAs) are specifically released by DCT resistant (DCTR) PCa clones and decrease the efficacy of DCT in PCa cells when overexpressed. Through bioinformatic analysis, we identified several potential targets of sDCTR-miRNAs’ activity including FOXO1, IGFBP3, and PDCD4 known to exert a role in DCT resistance. Additionally, we found that PPP2CB and INSIG1 mediated the ability of sDCTR-miRNAs to reduce the efficacy of DCT. We explored whether secreted sDCTR-miRNAs could affect the phenotype of PCa cells. We found that exposure to exosomes derived from DCTR PCa clones (in which the content of sDCTR-miRNAs was higher than in exosomes from parental cells), as well as exposure to exosome loaded with sDCTR-miRNAs, reduced the cytotoxicity of DCT in PCa cells sensitive to the drug. Finally, we validated circulating miR-183-5p and miR-21-5p as potential predictive biomarkers of DCT resistance in PCa patients. Our study suggests a horizontal transfer mechanism mediated by exosomal miRNAs that contributes to reduce docetaxel sensitivity and highlights the relevance of cell-to-cell communication in drug resistance.

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