Pharmacodynamics of tubulin and tubulin-binding agents: extending their potential beyond taxanes.

Abstract:

:Chemotherapeutic agents that disrupt the assembly or disassembly of microtubules, including paclitaxel and docetaxel, are among the most commonly prescribed anticancer therapies. However, the utility of taxane-based therapy is limited principally by problems with formulation, slow administration, cumulative neurotoxicity, and resistance in part through induction of P-glycoprotein. The broad-spectrum anticancer activity of taxane therapy has encouraged investigators to identify a class of structurally novel microtubulin-stabilizing agents that could produce comparable outcomes with fewer problems. Preclinical studies indicate that epothilones have a broad spectrum activity in paclitaxel-resistant breast cancer models. Several epothilone analogues have displayed promising antitumor activity in initial clinical trials. Ixabepilone, an epothilone derivative in the later stages of clinical development, has exhibited antitumor activity in breast cancers, with or without previous taxane therapy. The most common adverse events associated with ixabepilone are reversible sensory neuropathy and neutropenia. This review briefly outlines the basic science behind microtubule-targeting agents and examines the preclinical studies of several of these agents in breast cancer models. Also discussed are results from clinical trials of epothilones alone and in combination in patients with breast cancer.

journal_name

Clin Breast Cancer

journal_title

Clinical breast cancer

authors

Andreopoulou E,Muggia F

doi

10.3816/cbc.2008.s.001

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

S54-60

eissn

1526-8209

issn

1938-0666

pii

S1526-8209(11)70930-2

journal_volume

8 Suppl 2

pub_type

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