Details

Autor(en) / Beteiligte

• Jiménez, Natalia
• Reig, Òscar
• Montalbo, Ruth
• Milà-Guasch, Maria
• Nadal-Dieste, Lluis
• Castellano, Giancarlo
• Lozano, Juan José
• Victoria, Iván
• Font, Albert
• Rodriguez-Vida, Alejo
• Carles, Joan
• Suárez, Cristina
• Domènech, Montserrat
• Sala-González, Núria
• Fernández, Pedro Luis
• Rodríguez-Carunchio, Leonardo
• Díaz, Sherley
• Prat, Aleix
• Marín-Aguilera, Mercedes
• Mellado, Begoña

Titel

Cell Plasticity-Related Phenotypes and Taxanes Resistance in Castration-Resistant Prostate Cancer

Ist Teil von

• Frontiers in oncology, 2020-11, Vol.10, p.594023-594023

Ort / Verlag

Frontiers Research Foundation

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The prostatic tumor cells plasticity is involved in resistance to hormone-therapy, allowing these cells to survive despite androgen receptor inhibition. However, its role in taxanes resistance has not been fully established. Gene expression of plasticity-related phenotypes such as epithelial-mesenchymal transition (EMT), stem cell-like and neuroendocrine (NE) phenotypes was studied in vitro , in silico , in circulating tumor cells (CTCs) ( N =22) and in tumor samples ( N =117) from taxanes-treated metastatic castration-resistant prostate cancer (mCRPC) patients. Docetaxel (D)-resistant cells presented a more pronounced EMT phenotype than cabazitaxel (CZ)-resistant cells. In silico analysis revealed ESRP1 down-regulation in taxane-exposed mCRPC samples. Cell plasticity-related changes occurred in CTCs after taxanes treatment. Tumor EMT phenotype was associated with lower PSA progression-free survival (PFS) to D ( P <0.001), and better to CZ ( P =0.002). High ESRP1 expression was independently associated with longer PSA-PFS ( P <0.001) and radiologic-PFS ( P =0.001) in D and shorter PSA-PFS in the CZ cohort ( P =0.041). High SYP expression was independently associated with lower PSA-PFS in D ( P =0.003) and overall survival (OS) in CZ ( P =0.002), and high EZH2 expression was associated with adverse OS in D-treated patients ( P =0.013). In conclusion, EMT profile in primary tumor is differentially associated with D or CZ benefit and NE dedifferentiation correlates with adverse taxanes clinical outcome.