title: Androgen receptor on the move: boarding the microtubule expressway to the nucleus.
abstract: 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 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, as recent reports have revealed a connection between the microtubule-dependent trafficking of the androgen receptor 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 to identify individual patients more likely to respond to treatment.
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York 10065-4896, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Thadani-Mulero
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Giannakakou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D006801:Humans; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D043823:Taxoids