AR on the move; boarding the microtubule expressway to the nucleus

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-09, Vol.72 (18), p.4611-4615
• Main Authors: Thadani-Mulero, Maria, Nanus, David M., Giannakakou, Paraskevi
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-12-0783

Recent studies have shown that the microtubule-stabilizing drug, paclitaxel, which is commonly used for the treatment of prostate cancer inhibits signaling from the androgen receptor (AR) by inhibiting its nuclear accumulation downstream of microtubule stabilization. This mechanism is independent of paclitaxel-induced mitotic arrest and could provide an alternative mechanism of drug action that can explain its clinical activity. In this review, we highlight the importance of signaling and trafficking pathways that depend on intact and dynamic microtubules and as such they represent downstream targets of microtubule inhibitors. We showcase prostate cancer, which is driven by the activity of the androgen receptor (AR), as recent reports have revealed a connection between the microtubule-dependent trafficking of AR and the clinical efficacy of taxanes. Identification and further elucidation of microtubule-dependent tumor-specific pathways will help us better understand the molecular basis of clinical taxane resistance as well as identify individual patients more likely to respond to treatment.