Hypoxia and Noncoding RNAs in Taxane Resistance. (August 2018)

• Record Type: Journal Article
• Authors: Pucci, Perla; Rescigno, Pasquale; Sumanasuriya, Semini; de Bono, Johann; Crea, Francesco
• Is Part Of: Trends in pharmacological sciences. Volume 39:Number 8(2018)
• Page Start: 695
• Page End: 709
• Publication Date: 2018-08
• Subjects: Taxanes -- drug resistance -- hypoxia -- non-coding RNAs -- experimental therapies; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2018.05.002
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Taxanes are chemotherapeutic drugs employed in the clinic to treat a variety of malignancies. Despite their overall efficacy, cancer cells often display resistance to taxanes. Therefore, new strategies to increase the effectiveness of taxane-based chemotherapeutics are urgently needed. Multiple molecular players are linked to taxane resistance; these include efflux pumps, DNA repair mechanisms, and hypoxia-related pathways. In addition, emerging evidence indicates that both non-coding RNAs and epigenetic effectors might also be implicated in taxane resistance. Here we focus on the causes of taxane resistance, with the aim to envisage an integrated model of the 'taxane resistance phenome'. This model could help the development of novel therapeutic strategies to treat taxane-resistant neoplasms. Highlights: Taxanes are used to treat a variety of malignancies. However, taxane resistance is a major concern and understanding the causes of resistance could help the development of new therapies. Taxane resistance is a complex phenotype (a 'phenome') that requires the coordination of numerous molecular pathways. Hypoxia plays a central role in taxane resistance, by activating a transcriptional program that involves survival genes, ROS-shielding proteins, and DNA repair mechanisms. Recently, ncRNAs such as miRNAs and lncRNAs are emerging as key drivers of taxane resistance. These transcripts often interact with epigenetic effectors to modulate the phenotype of the cancer cell. Future research might identify other factors that cause taxane resistance. The new findings discussed here could pave the way for the development of more effective strategies to overcome taxane resistance.