title: Second generation taxanes: from the natural framework to the challenge of drug resistance.
abstract: Taxanes represent the most important class of antitumor agents introduced in cancer therapy in the last decade. The first member of the family was paclitaxel, firstly isolated from Taxus Brevifolia and found active as antitumor agent at the end of 60's. In the mid of 90's, a semi-synthetic taxane derived from 10-deacetylbaccatin III was introduced and thereafter named as docetaxel. Taxanes act by inhibiting microtubule dynamics, thereby inducing the arrest in M phase and the consequent activation of the apoptotic program. Since target of taxanes is not directly the genome, they are effective alone or in combination with DNA-damaging drugs in tumors not responding to conventional chemotherapeutics, such as advanced breast and non small cell lung cancer. In this review we will cover the aspects of clinical applications of the currently used taxanes as well as the clinical problems related to their use. Taking into consideration such problems, new taxanes have been developed in order to extend the spectrum of taxane-sensitive tumors and several of them are currently undergoing clinical trials. Among these agents, a newly developed taxane (BAY 59-8862) appears particularly interesting for the fact that it shows excellent oral bioavailability and activity in tumors with inherent resistance to paclitaxel.
authors.affiliation: Department of Obstetrics and Gynaecology, Università Cattolica Sacro Cuore, Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferlini
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Distefano
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
authors.forename: Antonella
authors.initials: A
authors.lastname: Riva
authors.forename: Paolo
authors.initials: P
authors.lastname: Morazzoni
authors.forename: Ezio
authors.initials: E
authors.lastname: Bombardelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mancuso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane