Epothilones: clinical update and future directions.
Epothilones are cytotoxic compounds that function in a similar fashion to paclitaxel and show promise for the treatment of a variety of cancers by inducing microtubule bundling and apoptotic cell death. However, their mechanism of microtubule binding is different from that of paclitaxel, which makes epothilones an attractive drug class for patients with taxane-resistant malignancies. As taxane resistance remains a significant barrier in the treatment of a variety of cancers, it is important to understand epothilones and their indications. Several epothilone compounds, including ixabepilone (BMS-247550, aza-epothilone B, Ixempra), patupilone (EPO906, epothilone B), KOS-862 (desoxyepothilone B, epothilone D), BMS-310705, ZK-EPO (ZK-219477), nd KOS-1584, have been testedf or the treatment of a variety of solid tumor types. Recently, ixabepilone became the first epothilone to be approved by the US Food and Drug Administration, for the treatment of metastatic or locally advanced breast cancer as monotherapy or in combination with capecitabine (Xeloda) after other treatments have failed. This article reviews recent findings from clinical trials of epothilones and discusses future directions for the use of these agents in cancer therapy, with a focus on the two most-studied epothilones to date: ixabepilone and patupilone.
Donovan
Diana
D
Weill Cornell Breast Center, Cornell University/ New York-Presbyterian Hospital, New York, NY 10021, USA. donovdi@med.cornell.edu
Vahdat
Linda T
LT
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone; C093788:epothilone B